Pharmaceutics

11 pages, 5736 KiB

Open AccessEditor’s ChoiceArticle

Co-Amorphization of Acemetacin with Basic Amino Acids as Co-Formers for Solubility Improvement and Gastric Ulcer Mitigation

by Jiayue Hou, Peixu Zhao, Yanfei Wang, Xiwei Jiang and Qiang Fu

Pharmaceutics 2024, 16(6), 745; https://doi.org/10.3390/pharmaceutics16060745 - 31 May 2024

Viewed by 303

Abstract

Acemetacin (ACM) is a new non-steroidal anti-inflammatory drug with anti-inflammatory, analgesic, and antipyretic effects. However, the poor water solubility and gastrointestinal side effects limit its use. Recently, the co-amorphous (CAM) strategy has attracted great interest to improve solubility for poorly water-soluble drugs, and [...] Read more.

Acemetacin (ACM) is a new non-steroidal anti-inflammatory drug with anti-inflammatory, analgesic, and antipyretic effects. However, the poor water solubility and gastrointestinal side effects limit its use. Recently, the co-amorphous (CAM) strategy has attracted great interest to improve solubility for poorly water-soluble drugs, and basic amino acids have the potential to protect the gastrointestinal tract. In order to develop a highly efficient and low-toxic ACM formulation, we prepared ACM CAM systems, with basic amino acids (lysine, arginine, and histidine) as co-formers, using a cryo-milling method. The solid-state behaviors of the ACM CAM systems were characterized by polarizing light microscopy, differential scanning calorimetry, and powder X-ray diffraction. Fourier transform infrared spectroscopy and molecular docking were carried out to understand the formation mechanism. Moreover, the gastro-protective effects of ACM CAM systems were evaluated in a rat gastric ulcer model. The results demonstrated that the CAM systems improved the dissolution rates of ACM compared with the neat amorphous counterpart. Furthermore, ACM CAM systems are significantly effective in mitigating the ACM-induced gastric ulcer in rats, and the ulcer inhibition rates were almost 90%. More importantly, this study provided a useful method for mitigating drug-induced gastrointestinal damage and broadened the applications of drug–amino acid CAM systems. Full article

(This article belongs to the Special Issue Formulation of Poorly Water-Soluble Drugs)

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34 pages, 2873 KiB

Open AccessEditor’s ChoiceReview

Chitosan Nanoparticles for Intranasal Drug Delivery

by Hossein Omidian, Erma J. Gill, Sumana Dey Chowdhury and Luigi X. Cubeddu

Pharmaceutics 2024, 16(6), 746; https://doi.org/10.3390/pharmaceutics16060746 - 31 May 2024

Viewed by 391

Abstract

This manuscript explores the use of nanostructured chitosan for intranasal drug delivery, targeting improved therapeutic outcomes in neurodegenerative diseases, psychiatric care, pain management, vaccination, and diabetes treatment. Chitosan nanoparticles are shown to enhance brain delivery, improve bioavailability, and minimize systemic side effects by [...] Read more.

This manuscript explores the use of nanostructured chitosan for intranasal drug delivery, targeting improved therapeutic outcomes in neurodegenerative diseases, psychiatric care, pain management, vaccination, and diabetes treatment. Chitosan nanoparticles are shown to enhance brain delivery, improve bioavailability, and minimize systemic side effects by facilitating drug transport across the blood–brain barrier. Despite substantial advancements in targeted delivery and vaccine efficacy, challenges remain in scalability, regulatory approval, and transitioning from preclinical studies to clinical applications. The future of chitosan-based nanomedicines hinges on advancing clinical trials, fostering interdisciplinary collaboration, and innovating in nanoparticle design to overcome these hurdles and realize their therapeutic potential. Full article

(This article belongs to the Special Issue Recent Advances in Nanoparticles for Mucosal Drug Delivery)

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28 pages, 12497 KiB

Open AccessEditor’s ChoiceReview

Atomic Force Microscopy for the Study of Cell Mechanics in Pharmaceutics

by Henrik Siboni, Ivana Ruseska and Andreas Zimmer

Pharmaceutics 2024, 16(6), 733; https://doi.org/10.3390/pharmaceutics16060733 - 29 May 2024

Viewed by 461

Abstract

Cell mechanics is gaining attraction in drug screening, but the applicable methods have not yet become part of the standardized norm. This review presents the current state of the art for atomic force microscopy, which is the most widely available method. The field [...] Read more.

Cell mechanics is gaining attraction in drug screening, but the applicable methods have not yet become part of the standardized norm. This review presents the current state of the art for atomic force microscopy, which is the most widely available method. The field is first motivated as a new way of tracking pharmaceutical effects, followed by a basic introduction targeted at pharmacists on how to measure cellular stiffness. The review then moves on to the current state of the knowledge in terms of experimental results and supplementary methods such as fluorescence microscopy that can give relevant additional information. Finally, rheological approaches as well as the theoretical interpretations are presented before ending on additional methods and outlooks. Full article

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17 pages, 3570 KiB

Open AccessEditor’s ChoiceReview

Review of Prodrug and Nanodelivery Strategies to Improve the Treatment of Colorectal Cancer with Fluoropyrimidine Drugs

by Santu Sarkar, Sezgin Kiren and William H. Gmeiner

Pharmaceutics 2024, 16(6), 734; https://doi.org/10.3390/pharmaceutics16060734 - 29 May 2024

Viewed by 467

Abstract

Fluoropyrimidine (FP) drugs are central components of combination chemotherapy regimens for the treatment of colorectal cancer (CRC). FP-based chemotherapy has improved survival outcomes over the last several decades with much of the therapeutic benefit derived from the optimization of dose and delivery. To [...] Read more.

Fluoropyrimidine (FP) drugs are central components of combination chemotherapy regimens for the treatment of colorectal cancer (CRC). FP-based chemotherapy has improved survival outcomes over the last several decades with much of the therapeutic benefit derived from the optimization of dose and delivery. To provide further advances in therapeutic efficacy, next-generation prodrugs and nanodelivery systems for FPs are being developed. This review focuses on recent innovative nanodelivery approaches for FP drugs that display therapeutic promise. We summarize established, clinically useful FP prodrug strategies, including capecitabine, which exploit tumor-specific enzyme expression for optimal anticancer activity. We then describe the use of FP DNA-based polymers (e.g., CF10) for the delivery of activated FP nucleotides as a nanodelivery approach with proven activity in pre-clinical models and with clinical potential. Multiple nanodelivery systems for FP delivery show promise in CRC pre-clinical models and we review advances in albumin-mediated FP delivery, the development of mesoporous silica nanoparticles, emulsion-based nanoparticles, metal nanoparticles, hydrogel-based delivery, and liposomes and lipid nanoparticles that display particular promise for therapeutic development. Nanodelivery of FPs is anticipated to impact CRC treatment in the coming years and to improve survival for cancer patients. Full article

(This article belongs to the Special Issue Recent Advances in Drug Delivery for the Treatment of Colorectal Cancer)

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18 pages, 10969 KiB

Open AccessEditor’s ChoiceArticle

Porous Chitosan/Hydroxyapatite Composite Microspheres for Vancomycin Loading and Releasing

by Meng-Ying Wu, Yi-Ting Kuo, I-Fang Kao and Shiow-Kang Yen

Pharmaceutics 2024, 16(6), 730; https://doi.org/10.3390/pharmaceutics16060730 - 29 May 2024

Viewed by 329

Abstract

Porous chitosan/hydroxyapatite (Chi-HAp) composite microspheres were prepared in an aqueous solution containing chitosan, calcium nitrate, and ammonium dihydrogen phosphate by using a hydrothermal method at various temperatures. The investigation indicated that temperature significantly impacted the final product’s appearance. Hydroxyapatite (HAp) coupled with dicalcium [...] Read more.

Porous chitosan/hydroxyapatite (Chi-HAp) composite microspheres were prepared in an aqueous solution containing chitosan, calcium nitrate, and ammonium dihydrogen phosphate by using a hydrothermal method at various temperatures. The investigation indicated that temperature significantly impacted the final product’s appearance. Hydroxyapatite (HAp) coupled with dicalcium phosphate dihydrate (DCPD) flakes were obviously found at 65 and 70 °C, while the latter gradually disappeared at higher temperatures. Conversely, synthesis at 90 °C led to smaller particle sizes due to the broken chitosan chains. The microspheres synthesized at 75 °C were selected for further analysis, revealing porous structures with specific surface areas of 36.66 m²/g, pores ranging from 3 to 100 nm, and pore volumes of 0.58 cm³/g. Vancomycin (VCM), an antibiotic, was then absorbed on and released from the microspheres derived at 75 °C, with a drug entrapment efficiency of 20% and a release duration exceeding 20 days. The bacteriostatic activity of the VCM/composite microspheres against Staphylococcus aureus increased with the VCM concentration and immersion time, revealing a stable inhibition zone diameter of approximately 4.3 mm from 24 to 96 h, and this indicated the retained stability and efficacy of the VCM during the encapsulating process. Full article

(This article belongs to the Special Issue Design of Mesoporous Materials for Biomedical Application)

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13 pages, 635 KiB

Open AccessEditor’s ChoiceReview

Current Progress in Magnetic Resonance-Guided Focused Ultrasound to Facilitate Drug Delivery across the Blood-Brain Barrier

by Ying Meng, Lorraine V. Kalia, Suneil K. Kalia, Clement Hamani, Yuexi Huang, Kullervo Hynynen, Nir Lipsman and Benjamin Davidson

Pharmaceutics 2024, 16(6), 719; https://doi.org/10.3390/pharmaceutics16060719 - 27 May 2024

Viewed by 491

Abstract

This review discusses the current progress in the clinical use of magnetic resonance-guided focused ultrasound (MRgFUS) and other ultrasound platforms to transiently permeabilize the blood-brain barrier (BBB) for drug delivery in neurological disorders and neuro-oncology. Safety trials in humans have followed on from [...] Read more.

This review discusses the current progress in the clinical use of magnetic resonance-guided focused ultrasound (MRgFUS) and other ultrasound platforms to transiently permeabilize the blood-brain barrier (BBB) for drug delivery in neurological disorders and neuro-oncology. Safety trials in humans have followed on from extensive pre-clinical studies, demonstrating a reassuring safety profile and paving the way for numerous translational clinical trials in Alzheimer’s disease, Parkinson’s disease, and primary and metastatic brain tumors. Future directions include improving ultrasound delivery devices, exploring alternative delivery approaches such as nanodroplets, and expanding the application to other neurological conditions. Full article

(This article belongs to the Special Issue Ultrasound-Mediated Blood–Brain Barrier Disruption and Drug Delivery)

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12 pages, 1988 KiB

Open AccessEditor’s ChoiceArticle

Structural Optimization of Carboxy-Terminal Phenylalanine-Modified Dendrimers for T-Cell Association and Model Drug Loading

by Hiroya Shiba, Tomoka Hirose, Akinobu Sakai, Ikuhiko Nakase, Akikazu Matsumoto and Chie Kojima

Pharmaceutics 2024, 16(6), 715; https://doi.org/10.3390/pharmaceutics16060715 - 27 May 2024

Viewed by 503

Abstract

Dendrimers are potent nanocarriers in drug delivery systems because their structure can be precisely controlled. We previously reported that polyamidoamine (PAMAM) dendrimers that were modified with 1,2-cyclohexanedicarboxylic acid (CHex) and phenylalanine (Phe), PAMAM-CHex-Phe, exhibited an effective association with various immune cells, including T-cells. [...] Read more.

Dendrimers are potent nanocarriers in drug delivery systems because their structure can be precisely controlled. We previously reported that polyamidoamine (PAMAM) dendrimers that were modified with 1,2-cyclohexanedicarboxylic acid (CHex) and phenylalanine (Phe), PAMAM-CHex-Phe, exhibited an effective association with various immune cells, including T-cells. In this study, we synthesized various carboxy-terminal Phe-modified dendrimers with different linkers using phthalic acid and linear dicarboxylic acids to determine the association of these dendrimers with Jurkat cells, a T-cell model. PAMAM-n-hexyl-Phe demonstrated the highest association with Jurkat T-cells. In addition, dendri-graft polylysine (DGL) with CHex and Phe, DGL-CHex-Phe, was synthesized, and its association with Jurkat cells was investigated. The association of DGL-CHex-Phe with T-cells was higher than that of PAMAM-CHex-Phe. However, it was insoluble in water and thus it is unsuitable as a drug carrier. Model drugs, such as protoporphyrin IX and paclitaxel, were loaded onto these dendrimers, and the most model drug molecules could be loaded into PAMAM-CHex-Phe. PTX-loaded PAMAM-CHex-Phe exhibited cytotoxicity against Jurkat cells at a similar level to free PTX. These results suggest that PAMAM-CHex-Phe exhibited both efficient T-cell association and drug loading properties. Full article

(This article belongs to the Special Issue Dendrimers: A Themed Issue in Honor of Professor Donald A. Tomalia on the Occasion of His 85th Birthday for His Outstanding Achievements in Advancing the Field of Dendrimers)

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17 pages, 3465 KiB

Open AccessEditor’s ChoiceArticle

In Vitro and In Vivo Synergetic Radiotherapy with Gold Nanoparticles and Docetaxel for Pancreatic Cancer

by Abdulaziz Alhussan, Nolan Jackson, Norman Chow, Ermias Gete, Nicole Wretham, Nancy Dos Santos, Wayne Beckham, Cheryl Duzenli and Devika B. Chithrani

Pharmaceutics 2024, 16(6), 713; https://doi.org/10.3390/pharmaceutics16060713 - 26 May 2024

Viewed by 670

Abstract

This research underscores the potential of combining nanotechnology with conventional therapies in cancer treatment, particularly for challenging cases like pancreatic cancer. We aimed to enhance pancreatic cancer treatment by investigating the synergistic effects of gold nanoparticles (GNPs) and docetaxel (DTX) as potential radiosensitizers [...] Read more.

This research underscores the potential of combining nanotechnology with conventional therapies in cancer treatment, particularly for challenging cases like pancreatic cancer. We aimed to enhance pancreatic cancer treatment by investigating the synergistic effects of gold nanoparticles (GNPs) and docetaxel (DTX) as potential radiosensitizers in radiotherapy (RT) both in vitro and in vivo, utilizing a MIA PaCa-2 monoculture spheroid model and NRG mice subcutaneously implanted with MIA PaCa-2 cells, respectively. Spheroids were treated with GNPs (7.5 μg/mL), DTX (100 nM), and 2 Gy of RT using a 6 MV linear accelerator. In parallel, mice received treatments of GNPs (2 mg/kg), DTX (6 mg/kg), and 5 Gy of RT (6 MV linear accelerator). In vitro results showed that though RT and DTX reduced spheroid size and increased DNA DSBs, the triple combination of DTX/RT/GNPs led to a significant 48% (p = 0.05) decrease in spheroid size and a 45% (p = 0.05) increase in DNA DSBs. In vivo results showed a 20% (p = 0.05) reduction in tumor growth 20 days post-treatment with (GNPs/RT/DTX) and an increase in mice median survival. The triple combination exhibited a synergistic effect, enhancing anticancer efficacy beyond individual treatments, and thus could be employed to improve radiotherapy and potentially reduce adverse effects. Full article

(This article belongs to the Special Issue Nanoparticle-Mediated Diagnostics and Drug Delivery Therapy)

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32 pages, 5508 KiB

Open AccessEditor’s ChoiceReview

Drug Development for Alzheimer’s and Parkinson’s Disease: Where Do We Go Now?

by Lisa Sequeira, Sofia Benfeito, Carlos Fernandes, Inês Lima, Joana Peixoto, Catarina Alves, Cláudia Sofia Machado, Alexandra Gaspar, Fernanda Borges and Daniel Chavarria

Pharmaceutics 2024, 16(6), 708; https://doi.org/10.3390/pharmaceutics16060708 - 24 May 2024

Viewed by 455

Abstract

Neurodegenerative diseases (NDs) are a set of progressive, chronic, and incurable diseases characterized by the gradual loss of neurons, culminating in the decline of cognitive and/or motor functions. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common NDs and represent an [...] Read more.

Neurodegenerative diseases (NDs) are a set of progressive, chronic, and incurable diseases characterized by the gradual loss of neurons, culminating in the decline of cognitive and/or motor functions. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common NDs and represent an enormous burden both in terms of human suffering and economic cost. The available therapies for AD and PD only provide symptomatic and palliative relief for a limited period and are unable to modify the diseases’ progression. Over the last decades, research efforts have been focused on developing new pharmacological treatments for these NDs. However, to date, no breakthrough treatment has been discovered. Hence, the development of disease-modifying drugs able to halt or reverse the progression of NDs remains an unmet clinical need. This review summarizes the major hallmarks of AD and PD and the drugs available for pharmacological treatment. It also sheds light on potential directions that can be pursued to develop new, disease-modifying drugs to treat AD and PD, describing as representative examples some advances in the development of drug candidates targeting oxidative stress and adenosine A2A receptors. Full article

(This article belongs to the Special Issue The Therapy of Alzheimer’s Disease: Towards a New Generation of Drugs)

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41 pages, 2380 KiB

Open AccessEditor’s ChoiceReview

Insight into the Functional Dynamics and Challenges of Exosomes in Pharmaceutical Innovation and Precision Medicine

by Anu Sharma, Anita Yadav, Aparajita Nandy and Subhadip Ghatak

Pharmaceutics 2024, 16(6), 709; https://doi.org/10.3390/pharmaceutics16060709 - 24 May 2024

Viewed by 617

Abstract

Of all the numerous nanosized extracellular vesicles released by a cell, the endosomal-originated exosomes are increasingly recognized as potential therapeutics, owing to their inherent stability, low immunogenicity, and targeted delivery capabilities. This review critically evaluates the transformative potential of exosome-based modalities across pharmaceutical [...] Read more.

Of all the numerous nanosized extracellular vesicles released by a cell, the endosomal-originated exosomes are increasingly recognized as potential therapeutics, owing to their inherent stability, low immunogenicity, and targeted delivery capabilities. This review critically evaluates the transformative potential of exosome-based modalities across pharmaceutical and precision medicine landscapes. Because of their precise targeted biomolecular cargo delivery, exosomes are posited as ideal candidates in drug delivery, enhancing regenerative medicine strategies, and advancing diagnostic technologies. Despite the significant market growth projections of exosome therapy, its utilization is encumbered by substantial scientific and regulatory challenges. These include the lack of universally accepted protocols for exosome isolation and the complexities associated with navigating the regulatory environment, particularly the guidelines set forth by the U.S. Food and Drug Administration (FDA). This review presents a comprehensive overview of current research trajectories aimed at addressing these impediments and discusses prospective advancements that could substantiate the clinical translation of exosomal therapies. By providing a comprehensive analysis of both the capabilities and hurdles inherent to exosome therapeutic applications, this article aims to inform and direct future research paradigms, thereby fostering the integration of exosomal systems into mainstream clinical practice. Full article

(This article belongs to the Special Issue Extracellular Vesicle-Based Drug Delivery Systems)

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24 pages, 7549 KiB

Open AccessEditor’s ChoiceArticle

Focused Ultrasound-Mediated Disruption of the Blood–Brain Barrier for AAV9 Delivery in a Mouse Model of Huntington’s Disease

by Bernie S. Owusu-Yaw, Yongzhi Zhang, Lilyan Garrett, Alvin Yao, Kai Shing, Ana Rita Batista, Miguel Sena-Esteves, Jaymin Upadhyay, Kimberly Kegel-Gleason and Nick Todd

Pharmaceutics 2024, 16(6), 710; https://doi.org/10.3390/pharmaceutics16060710 - 24 May 2024

Viewed by 494

Abstract

Huntington’s disease (HD) is a monogenic neurodegenerative disorder caused by a cytosine–adenine–guanine (CAG) trinucleotide repeat expansion in the HTT gene. There are no cures for HD, but the genetic basis of this disorder makes gene therapy a viable approach. Adeno-associated virus (AAV)-miRNA-based therapies [...] Read more.

Huntington’s disease (HD) is a monogenic neurodegenerative disorder caused by a cytosine–adenine–guanine (CAG) trinucleotide repeat expansion in the HTT gene. There are no cures for HD, but the genetic basis of this disorder makes gene therapy a viable approach. Adeno-associated virus (AAV)-miRNA-based therapies have been demonstrated to be effective in lowering HTT mRNA; however, the blood–brain barrier (BBB) poses a significant challenge for gene delivery to the brain. Delivery strategies include direct injections into the central nervous system, which are invasive and can result in poor diffusion of viral particles through the brain parenchyma. Focused ultrasound (FUS) is an alternative approach that can be used to non-invasively deliver AAVs by temporarily disrupting the BBB. Here, we investigate FUS-mediated delivery of a single-stranded AAV9 bearing a cDNA for GFP in 2-month-old wild-type mice and the zQ175 HD mouse model at 2-, 6-, and 12-months. FUS treatment improved AAV9 delivery for all mouse groups. The delivery efficacy was similar for all WT and HD groups, with the exception of the zQ175 12-month cohort, where we observed decreased GFP expression. Astrocytosis did not increase after FUS treatment, even within the zQ175 12-month group exhibiting higher baseline levels of GFAP expression. These findings demonstrate that FUS can be used to non-invasively deliver an AAV9-based gene therapy to targeted brain regions in a mouse model of Huntington’s disease. Full article

(This article belongs to the Section Drug Delivery and Controlled Release)

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34 pages, 1507 KiB

Open AccessEditor’s ChoiceReview

Process Simulation of Twin-Screw Granulation: A Review

by Tony Bediako Arthur and Nejat Rahmanian

Pharmaceutics 2024, 16(6), 706; https://doi.org/10.3390/pharmaceutics16060706 - 24 May 2024

Viewed by 819

Abstract

Twin-screw granulation has emerged as a key process in powder processing industries and in the pharmaceutical sector to produce granules with controlled properties. This comprehensive review provides an overview of the simulation techniques and approaches that have been employed in the study of [...] Read more.

Twin-screw granulation has emerged as a key process in powder processing industries and in the pharmaceutical sector to produce granules with controlled properties. This comprehensive review provides an overview of the simulation techniques and approaches that have been employed in the study of twin-screw granulation processes. This review discusses the major aspects of the twin-screw granulation process which include the fundamental principles of twin-screw granulation, equipment design, process parameters, and simulation methodologies. It highlights the importance of operating conditions and formulation designs in powder flow dynamics, mixing behaviour, and particle interactions within the twin-screw granulator for enhancing product quality and process efficiency. Simulation techniques such as the population balance model (PBM), computational fluid dynamics (CFD), the discrete element method (DEM), process modelling software (PMS), and other coupled techniques are critically discussed with a focus on simulating twin-screw granulation processes. This paper examines the challenges and limitations associated with each simulation approach and provides insights into future research directions. Overall, this article serves as a valuable resource for researchers who intend to develop their understanding of twin-screw granulation and provides insights into the various techniques and approaches available for simulating the twin-screw granulation process. Full article

(This article belongs to the Special Issue Pharmaceutical Solids: Advanced Manufacturing and Characterization)

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17 pages, 4839 KiB

Open AccessEditor’s ChoiceArticle

Risperidone-Loaded Nasal Thermosensitive Polymeric Micelles: Quality by Design-Based Formulation Study

by Bence Sipos, Gábor Katona and Ildikó Csóka

Pharmaceutics 2024, 16(6), 703; https://doi.org/10.3390/pharmaceutics16060703 - 24 May 2024

Viewed by 495

Abstract

The current research aims to develop thermosensitive polymeric micelles loaded with risperidone for nasal administration, emphasizing the added benefits of their thermosensitive behavior under nasal conditions. An initial risk assessment facilitated the advanced development process, confirming that the key indicators of thermosensitivity were [...] Read more.

The current research aims to develop thermosensitive polymeric micelles loaded with risperidone for nasal administration, emphasizing the added benefits of their thermosensitive behavior under nasal conditions. An initial risk assessment facilitated the advanced development process, confirming that the key indicators of thermosensitivity were suitable for nasal application. The polymeric micelles exhibited an average size of 118.4 ± 3.1 nm at ambient temperature and a size of 20.47 ± 1.2 nm at 36.5 °C, in both cases in monodisperse distribution. Factors such as pH and viscosity did not significantly impact these parameters, demonstrating appropriate nasal applicability. The model formulations showed a rapid, burst-like drug release profile in vitro, accompanied by a quick and high permeation rate at nasal conditions. Overall, the Quality by Design-based risk assessment process led to the development of an advanced drug delivery system capable of administering risperidone through the nasal cavity. Full article

(This article belongs to the Special Issue Nasal Drug Delivery: Challenges and Future Opportunities)

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27 pages, 4655 KiB

Open AccessEditor’s ChoiceReview

Complex Emulsions as an Innovative Pharmaceutical Dosage form in Addressing the Issues of Multi-Drug Therapy and Polypharmacy Challenges

by Naresh Yandrapalli

Pharmaceutics 2024, 16(6), 707; https://doi.org/10.3390/pharmaceutics16060707 - 24 May 2024

Viewed by 571

Abstract

This review explores the intersection of microfluidic technology and complex emulsion development as a promising solution to the challenges of formulations in multi-drug therapy (MDT) and polypharmacy. The convergence of microfluidic technology and complex emulsion fabrication could herald a transformative era in multi-drug [...] Read more.

This review explores the intersection of microfluidic technology and complex emulsion development as a promising solution to the challenges of formulations in multi-drug therapy (MDT) and polypharmacy. The convergence of microfluidic technology and complex emulsion fabrication could herald a transformative era in multi-drug delivery systems, directly confronting the prevalent challenges of polypharmacy. Microfluidics, with its unparalleled precision in droplet formation, empowers the encapsulation of multiple drugs within singular emulsion particles. The ability to engineer emulsions with tailored properties—such as size, composition, and release kinetics—enables the creation of highly efficient drug delivery vehicles. Thus, this innovative approach not only simplifies medication regimens by significantly reducing the number of necessary doses but also minimizes the pill burden and associated treatment termination—issues associated with polypharmacy. It is important to bring forth the opportunities and challenges of this synergy between microfluidic-driven complex emulsions and multi-drug therapy poses. Together, they not only offer a sophisticated method for addressing the intricacies of delivering multiple drugs but also align with broader healthcare objectives of enhancing treatment outcomes, patient safety, and quality of life, underscoring the importance of dosage form innovations in tackling the multifaceted challenges of modern pharmacotherapy. Full article

(This article belongs to the Special Issue Micro- and Nano-Emulsions as Drug Delivery Systems)

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17 pages, 13618 KiB

Open AccessEditor’s ChoiceArticle

Cytotoxic and Immunomodulatory Effects of Hypericin as a Photosensitizer in Photodynamic Therapy Used on Skin Cell Cultures

by Magdalena Krupka-Olek, Andrzej Bożek, Zenon P. Czuba, Małgorzata Kłósek, Grzegorz Cieślar and Aleksandra Kawczyk-Krupka

Pharmaceutics 2024, 16(6), 696; https://doi.org/10.3390/pharmaceutics16060696 - 23 May 2024

Viewed by 497

Abstract

Determination of the hypericin–photodynamic (HY–PDT) effect on the secretion of cytokines secreted by the skin cells, may be the basis for using the immunomodulatory effect of photodynamic action in the treatment of inflammatory skin diseases. The study aimed to evaluate the cytotoxic and [...] Read more.

Determination of the hypericin–photodynamic (HY–PDT) effect on the secretion of cytokines secreted by the skin cells, may be the basis for using the immunomodulatory effect of photodynamic action in the treatment of inflammatory skin diseases. The study aimed to evaluate the cytotoxic and immunomodulatory effects of hypericin (HY) in photodynamic therapy (PDT) performed in vitro on cultures of selected skin cell lines. The study used two human cell lines, primary dermal fibroblast (HDFa) and primary epidermal keratinocytes (HEKa). The MTT test was used to define the metabolic activity of treated cells. Cell supernatants subjected to sublethal PDT were assessed to determine the interleukins: IL-2, IL-8, IL-10, IL-11, IL-19, IL-22, and metalloproteinase 1 (MMP-1). The results confirm the destructive effect of HY–PDT and the immunomodulatory effects of sublethal doses on the selected skin cells, depending on the concentration of HY and the light doses. No statistically significant differences were noted in IL-2 and IL-10 concentration after HY–PDT for HEKa and HDFa lines. After using HY–PDT, the concentration of IL-8, MMP-1, IL-22, and IL-11 significantly decreased in the HEKa line. Moreover, the concentration of IL-19 and MMP-1 significantly decreased in the HDFa line. The concentration of IL-11 in the HDFa line after using only the HY, without the light, increased but decreased after HY–PDT. Our experiment confirmed that HY–PDT has not only a cytotoxic effect but, used in sublethal doses, also presents immunomodulatory properties. These may be an advantage of HY–PDT when used in the treatment of persistent skin inflammation, connected with the release of pro-inflammatory cytokines resistant to conventional treatment methods. Full article

(This article belongs to the Special Issue Natural Products in Photodynamic Therapy)

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23 pages, 1109 KiB

Open AccessEditor’s ChoiceReview

Emerging Trends in Bilosomes as Therapeutic Drug Delivery Systems

by Hemlata Kaurav, Meenakshi Tripathi, Simran Deep Kaur, Amit Bansal, Deepak N. Kapoor and Sandeep Sheth

Pharmaceutics 2024, 16(6), 697; https://doi.org/10.3390/pharmaceutics16060697 - 23 May 2024

Viewed by 524

Abstract

In recent years, there has been a notable surge in the utilization of stabilized bile acid liposomes, chemical conjugates, complexes, mixed micelles, and other drug delivery systems derived from bile acids, often referred to as bilosomes. The molecular structure and interactions of these [...] Read more.

In recent years, there has been a notable surge in the utilization of stabilized bile acid liposomes, chemical conjugates, complexes, mixed micelles, and other drug delivery systems derived from bile acids, often referred to as bilosomes. The molecular structure and interactions of these amphiphilic compounds provide a distinctive and captivating subject for investigation. The enhanced stability of new generation bilosomes inside the gastrointestinal system results in the prevention of drug degradation and an improvement in mucosal penetration. These characteristics render bilosomes to be a prospective nanocarrier for pharmaceutical administration, prompting researchers to investigate their potential in other domains. This review paper discusses bilosomes that have emerged as a viable modality in the realm of drug delivery and have significant promise for use across several domains. Moreover, this underscores the need for additional investigation and advancement in order to comprehensively comprehend the prospective uses of bilosomes and their effectiveness in the field of pharmaceutical administration. This review study explores the current scholarly attention on bilosomes as prospective carriers for drug delivery. Therapeutic areas where bilosomes have shown outstanding performance in terms of drug delivery are outlined in the graphical abstract. Full article

(This article belongs to the Special Issue The 15th Anniversary of Pharmaceutics—Advances and Future Trends in Drug Delivery)

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22 pages, 6720 KiB

Open AccessEditor’s ChoiceArticle

Archaeosomes for Oral Drug Delivery: From Continuous Microfluidics Production to Powdered Formulations

by Ivan Vidakovic, Karin Kornmueller, Daniela Fiedler, Johannes Khinast, Eleonore Fröhlich, Gerd Leitinger, Christina Horn, Julian Quehenberger, Oliver Spadiut and Ruth Prassl

Pharmaceutics 2024, 16(6), 694; https://doi.org/10.3390/pharmaceutics16060694 - 23 May 2024

Viewed by 532

Abstract

Archaeosomes were manufactured from natural archaeal lipids by a microfluidics-assisted single-step production method utilizing a mixture of di- and tetraether lipids extracted from Sulfolobus acidocaldarius. The primary aim of this study was to investigate the exceptional stability of archaeosomes as potential carriers for [...] Read more.

Archaeosomes were manufactured from natural archaeal lipids by a microfluidics-assisted single-step production method utilizing a mixture of di- and tetraether lipids extracted from Sulfolobus acidocaldarius. The primary aim of this study was to investigate the exceptional stability of archaeosomes as potential carriers for oral drug delivery, with a focus on powdered formulations. The archaeosomes were negatively charged with a size of approximately 100 nm and a low polydispersity index. To assess their suitability for oral delivery, the archaeosomes were loaded with two model drugs: calcein, a fluorescent compound, and insulin, a peptide hormone. The archaeosomes demonstrated high stability in simulated intestinal fluids, with only 5% of the encapsulated compounds being released after 24 h, regardless of the presence of degrading enzymes or extremely acidic pH values such as those found in the stomach. In a co-culture cell model system mimicking the intestinal barrier, the archaeosomes showed strong adhesion to the cell membranes, facilitating a slow release of contents. The archaeosomes were loaded with insulin in a single-step procedure achieving an encapsulation efficiency of approximately 35%. These particles have been exposed to extreme manufacturing temperatures during freeze-drying and spray-drying processes, demonstrating remarkable resilience under these harsh conditions. The fabrication of stable dry powder formulations of archaeosomes represents a promising advancement toward the development of solid dosage forms for oral delivery of biological drugs. Full article

(This article belongs to the Special Issue Advances in Oral Administration)

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13 pages, 1872 KiB

Open AccessEditor’s ChoiceArticle

Population Pharmacokinetic Analysis and Simulation of Alternative Dosing Regimens for Biosimilars to Adalimumab and Etanercept in Patients with Rheumatoid Arthritis

by Stephanie F. Ling, Kayode Ogungbenro, Adam S. Darwich, Amirah Binti Mohammad Ariff, Nisha Nair, James Bluett, Ann W. Morgan, John D. Isaacs, Anthony G. Wilson, Kimme L. Hyrich, Anne Barton and Darren Plant

Pharmaceutics 2024, 16(6), 702; https://doi.org/10.3390/pharmaceutics16060702 - 23 May 2024

Viewed by 448

Abstract

Efficacy to biologics in rheumatoid arthritis (RA) patients is variable and is likely influenced by each patient’s circulating drug levels. Using modelling and simulation, the aim of this study was to investigate whether adalimumab and etanercept biosimilar dosing intervals can be altered to [...] Read more.

Efficacy to biologics in rheumatoid arthritis (RA) patients is variable and is likely influenced by each patient’s circulating drug levels. Using modelling and simulation, the aim of this study was to investigate whether adalimumab and etanercept biosimilar dosing intervals can be altered to achieve therapeutic drug levels at a faster/similar time compared to the recommended interval. RA patients starting subcutaneous Amgevita or Benepali (adalimumab and etanercept biosimilars, respectively) were recruited and underwent sparse serum sampling for drug concentrations. Drug levels were measured using commercially available kits. Pharmacokinetic data were analysed using a population approach (popPK) and potential covariates were investigated in models. Models were compared using goodness-of-fit criteria. Final models were selected and used to simulate alternative dosing intervals. Ten RA patients starting the adalimumab biosimilar and six patients starting the etanercept biosimilar were recruited. One-compartment PK models were used to describe the popPK models for both drugs; no significant covariates were found. Typical individual parameter estimates were used to simulate altered dosing intervals for both drugs. A simulation of dosing the etanercept biosimilar at a lower rate of every 10 days reached steady-state concentrations earlier than the usual dosing rate of every 7 days. Simulations of altered dosing intervals could form the basis for future personalised dosing studies, potentially saving costs whilst increasing efficacy. Full article

(This article belongs to the Special Issue Population Pharmacokinetics and Its Clinical Applications)

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37 pages, 4780 KiB

Open AccessEditor’s ChoiceReview

Unlocking the Potential of Oleanolic Acid: Integrating Pharmacological Insights and Advancements in Delivery Systems

by Muhammad Wasim and Maria Camilla Bergonzi

Pharmaceutics 2024, 16(6), 692; https://doi.org/10.3390/pharmaceutics16060692 - 21 May 2024

Viewed by 542

Abstract

The growing interest in oleanolic acid (OA) as a triterpenoid with remarkable health benefits prompts an emphasis on its efficient use in pharmaceutical research. OA exhibits a range of pharmacological effects, including antidiabetic, anti-inflammatory, immune-enhancing, gastroprotective, hepatoprotective, antitumor, and antiviral properties. While OA [...] Read more.

The growing interest in oleanolic acid (OA) as a triterpenoid with remarkable health benefits prompts an emphasis on its efficient use in pharmaceutical research. OA exhibits a range of pharmacological effects, including antidiabetic, anti-inflammatory, immune-enhancing, gastroprotective, hepatoprotective, antitumor, and antiviral properties. While OA demonstrates diverse pharmacological effects, optimizing its therapeutic potential requires overcoming significant challenges. In the field of pharmaceutical research, the exploration of efficient drug delivery systems is essential to maximizing the therapeutic potential of bioactive compounds. Efficiently delivering OA faces challenges, such as poor aqueous solubility and restricted bioavailability, and to unlock its full therapeutic efficacy, novel formulation strategies are imperative. This discussion thoroughly investigates different approaches and advancements in OA drug delivery systems with the aim of enhancing the biopharmaceutical features and overall efficacy in diverse therapeutic contexts. Full article

(This article belongs to the Special Issue Novel Drug Delivery Systems of Phytomedicines)

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16 pages, 4439 KiB

Open AccessEditor’s ChoiceArticle

Fabrication of Ciprofloxacin-Loaded Sodium Alginate Nanobeads Coated with Thiol-Anchored Chitosan Using B-390 Encapsulator Following Optimization by DoE

by Mahwash Mukhtar, Ildikó Csóka, Josipa Martinović, Gordana Šelo, Ana Bucić-Kojić, László Orosz, Dóra Paróczai, Katalin Burian and Rita Ambrus

Pharmaceutics 2024, 16(6), 691; https://doi.org/10.3390/pharmaceutics16060691 - 21 May 2024

Viewed by 653

Abstract

Most infectious diseases of the gastrointestinal tract can easily be treated by exploiting the already available antibiotics with the change in administration approach and delivery system. Ciprofloxacin (CIP) is used as a drug of choice for many bacterial infections; however, long-term therapy and [...] Read more.

Most infectious diseases of the gastrointestinal tract can easily be treated by exploiting the already available antibiotics with the change in administration approach and delivery system. Ciprofloxacin (CIP) is used as a drug of choice for many bacterial infections; however, long-term therapy and off-site drug accumulation lead to an increased risk of tendinitis and peripheral neuropathy. To overcome this issue, nanotechnology is being exploited to encapsulate antibiotics within polymeric structures, which not only facilitates dose maintenance at the infection site but also limits off-site side effects. Here, sodium alginate (SA) and thiol-anchored chitosan (TC) were used to encapsulate CIP via a calcium chloride (CaCl₂) cross-linker. For this purpose, the B-390 encapsulator was employed in the preparation of nanobeads using a simple technique. The hydrogel-like sample was then freeze-dried, using trehalose or mannitol as a lyoprotectant, to obtain a fine dry powder. Design of Experiment (DoE) was utilized to optimize the nanobead production, in which the influence of different independent variables was studied for their outcome on the polydispersity index (PDI), particle size, zeta potential, and percentage encapsulation efficiency (% EE). In vitro dissolution studies were performed in simulated saliva fluid, simulated gastric fluid, and simulated intestinal fluid. Antibacterial and anti-inflammatory studies were also performed along with cytotoxicity profiling. By and large, the study presented positive outcomes, proving the advantage of using nanotechnology in fabricating new delivery approaches using already available antibiotics. Full article

(This article belongs to the Special Issue Editorial Board Members’ Collection Series: Chitosan in Biomedicine: Current Status, Future Perspectives and Challenges)

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22 pages, 5653 KiB

Open AccessEditor’s ChoiceArticle

Effects of Nozzle Retraction Elimination on Spray Distribution in Middle-Posterior Turbinate Regions: A Comparative Study

by Amr Seifelnasr, Xiuhua Si and Jinxiang Xi

Pharmaceutics 2024, 16(5), 683; https://doi.org/10.3390/pharmaceutics16050683 - 19 May 2024

Viewed by 504

Abstract

The standard multi-dose nasal spray pump features an integrated actuator and nozzle, which inevitably causes a retraction of the nozzle tip during application. The retraction stroke is around 5.5 mm and drastically reduces the nozzle’s insertion depth, which further affects the initial nasal [...] Read more.

The standard multi-dose nasal spray pump features an integrated actuator and nozzle, which inevitably causes a retraction of the nozzle tip during application. The retraction stroke is around 5.5 mm and drastically reduces the nozzle’s insertion depth, which further affects the initial nasal spray deposition and subsequent translocation, potentially increasing drug wastes and dosimetry variability. To address this issue, we designed a new spray pump that separated the nozzle from the actuator and connected them with a flexible tube, thereby eliminating nozzle retraction during application. The objective of this study is to test the new device’s performance in comparison to the conventional nasal pump in terms of spray generation, plume development, and dosimetry distribution. For both devices, the spray droplet size distribution was measured using a laser diffraction particle analyzer. Plume development was recorded with a high-definition camera. Nasal dosimetry was characterized in two transparent nasal cavity casts (normal and decongested) under two breathing conditions (breath-holding and constant inhalation). The nasal formulation was a 0.25% w/v methyl cellulose aqueous solution with a fluorescent dye. For each test case, the temporospatial spray translocation in the nasal cavity was recorded, and the final delivered doses were quantified in five nasal regions. The results indicate minor differences in droplet size distribution between the two devices. The nasal plume from the new device presents a narrower plume angle. The head orientation, the depth at which the nozzle is inserted into the nostril, and the administration angle play crucial roles in determining the initial deposition of nasal sprays as well as the subsequent translocation of the liquid film/droplets. Quantitative measurements of deposition distributions in the nasal models were augmented with visualization recordings to evaluate the delivery enhancements introduced by the new device. With an extension tube, the modified device produced a lower spray output and delivered lower doses in the front, middle, and back turbinate than the conventional nasal pump. However, sprays from the new device were observed to penetrate deeper into the nasal passages, predominantly through the middle-upper meatus. This resulted in consistently enhanced dosing in the middle-upper turbinate regions while at the cost of higher drug loss to the pharynx. Full article

(This article belongs to the Special Issue Challenges and Innovative Solutions in Nasal Drug Delivery: From Formulation Development to Mode of Administration, 2nd Edition)

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13 pages, 604 KiB

Open AccessEditor’s ChoicePerspective

Therapeutic Drug Monitoring and Biomarkers; towards Better Dosing of Antimicrobial Therapy

by Eman Wehbe, Asad E. Patanwala, Christine Y. Lu, Hannah Yejin Kim, Sophie L. Stocker and Jan-Willem C. Alffenaar

Pharmaceutics 2024, 16(5), 677; https://doi.org/10.3390/pharmaceutics16050677 - 17 May 2024

Viewed by 715

Abstract

Due to variability in pharmacokinetics and pharmacodynamics, clinical outcomes of antimicrobial drug therapy vary between patients. As such, personalised medication management, considering both pharmacokinetics and pharmacodynamics, is a growing concept of interest in the field of infectious diseases. Therapeutic drug monitoring is used [...] Read more.

Due to variability in pharmacokinetics and pharmacodynamics, clinical outcomes of antimicrobial drug therapy vary between patients. As such, personalised medication management, considering both pharmacokinetics and pharmacodynamics, is a growing concept of interest in the field of infectious diseases. Therapeutic drug monitoring is used to adjust and individualise drug regimens until predefined pharmacokinetic exposure targets are achieved. Minimum inhibitory concentration (drug susceptibility) is the best available pharmacodynamic parameter but is associated with many limitations. Identification of other pharmacodynamic parameters is necessary. Repurposing diagnostic biomarkers as pharmacodynamic parameters to evaluate treatment response is attractive. When combined with therapeutic drug monitoring, it could facilitate making more informed dosing decisions. We believe the approach has potential and justifies further research. Full article

(This article belongs to the Special Issue Therapeutic Drug Monitoring and Pharmacokinetics-Based Individualization of Drug Therapy, 2nd Edition)

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11 pages, 1641 KiB

Open AccessEditor’s ChoiceArticle

Suitable Promoter for DNA Vaccination Using a pDNA Ternary Complex

by Tomoaki Kurosaki, Hiroki Nakamura, Hitoshi Sasaki and Yukinobu Kodama

Pharmaceutics 2024, 16(5), 679; https://doi.org/10.3390/pharmaceutics16050679 - 17 May 2024

Viewed by 603

Abstract

In this study, we evaluated the effect of several promoters on the transfection activity and immune-induction efficiency of a plasmid DNA (pDNA)/polyethylenimine/γ-polyglutamic acid complex (pDNA ternary complex). Model pDNAs encoding firefly luciferase (Luc) were constructed with several promoters, such as simian virus 40 [...] Read more.

In this study, we evaluated the effect of several promoters on the transfection activity and immune-induction efficiency of a plasmid DNA (pDNA)/polyethylenimine/γ-polyglutamic acid complex (pDNA ternary complex). Model pDNAs encoding firefly luciferase (Luc) were constructed with several promoters, such as simian virus 40 (SV40), eukaryotic elongation factor 1 alpha (EF1), cytomegalovirus (CMV), and chicken beta actin hybrid (CBh) (pSV40-Luc, pEF1-Luc, pCMV-Luc, and pCBh-Luc, respectively). Four types of pDNA ternary complexes, each with approximately 145-nm particle size and −30-mV ζ-potential, were stably constructed. The pDNA ternary complex containing pSV40-Luc showed low gene expression, but the other complexes containing pEF1-Luc, pCMV-Luc, and pCBh-Luc showed high gene expression in DC2.4 cells and spleen after intravenous administration. After immunization using various pDNA encoding ovalbumin (OVA) such as pEF1-OVA, pCMV-OVA, and pCBh-OVA, only the pDNA ternary complex containing pCBh-OVA showed significant anti-OVA immunoglobulin G (IgG) induction. In conclusion, our results showed that the CBh promoter is potentially suitable for use in pDNA ternary complex-based DNA vaccination. Full article

(This article belongs to the Special Issue Plasmid DNA for Gene Therapy and DNA Vaccine Applications, 2nd Edition)

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27 pages, 5074 KiB

Open AccessEditor’s ChoiceReview

Strategies to Improve the Transdermal Delivery of Poorly Water-Soluble Non-Steroidal Anti-Inflammatory Drugs

by Alexandra Balmanno, James R. Falconer, Halley G. Ravuri and Paul C. Mills

Pharmaceutics 2024, 16(5), 675; https://doi.org/10.3390/pharmaceutics16050675 - 16 May 2024

Viewed by 802

Abstract

The transdermal delivery of non-steroidal anti-inflammatory drugs (NSAIDs) has the potential to overcome some of the major disadvantages relating to oral NSAID usage, such as gastrointestinal adverse events and compliance. However, the poor solubility of many of the newer NSAIDs creates challenges in [...] Read more.

The transdermal delivery of non-steroidal anti-inflammatory drugs (NSAIDs) has the potential to overcome some of the major disadvantages relating to oral NSAID usage, such as gastrointestinal adverse events and compliance. However, the poor solubility of many of the newer NSAIDs creates challenges in incorporating the drugs into formulations suitable for application to skin and may limit transdermal permeation, particularly if the goal is therapeutic systemic drug concentrations. This review is an overview of the various strategies used to increase the solubility of poorly soluble NSAIDs and enhance their permeation through skin, such as the modification of the vehicle, the modification of or bypassing the barrier function of the skin, and using advanced nano-sized formulations. Furthermore, the simple yet highly versatile microemulsion system has been found to be a cost-effective and highly successful technology to deliver poorly water-soluble NSAIDs. Full article

(This article belongs to the Special Issue 15th Anniversary of Pharmaceutics—Improvement of Drug Bioavailability)

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15 pages, 23424 KiB

Open AccessEditor’s ChoiceArticle

The Proteasome Inhibitor CEP-18770 Induces Cell Death in Medulloblastoma

by Swastina Nath Varma, Shany Ye, Sara Ferlin, Charley Comer, Kian Cotton and Maria Victoria Niklison-Chirou

Pharmaceutics 2024, 16(5), 672; https://doi.org/10.3390/pharmaceutics16050672 - 16 May 2024

Viewed by 751

Abstract

Medulloblastomas (MBs) represent the most prevalent malignant solid tumors in kids. The conventional treatment regimen for MBs includes surgical removal of the tumor, followed by radiation and chemotherapy. However, this approach is associated with significant morbidity and detrimental side effects. Consequently, there is [...] Read more.

Medulloblastomas (MBs) represent the most prevalent malignant solid tumors in kids. The conventional treatment regimen for MBs includes surgical removal of the tumor, followed by radiation and chemotherapy. However, this approach is associated with significant morbidity and detrimental side effects. Consequently, there is a critical demand for more precise and less harmful treatments to enhance the quality of life for survivors. CEP-18770, a novel proteasome inhibitor that targets the 20S subunit, has emerged as a promising candidate, due to its anticancer activity in metastatic solid tumors and multiple myeloma, coupled with an acceptable safety profile. In this study, we aimed to assess the anticancer efficacy of CEP-18770 by employing a variety of MB patient-derived cells and cell lines. Our preclinical investigations revealed that CEP-18770 effectively inhibits proteasome activity and induces apoptosis in MBs cells. Furthermore, we discovered that CEP-18770 and cisplatin, a current component of MB therapy, exhibit a synergistic apoptotic effect. This paper shows that CEP-18770 holds potential as an adjunctive treatment for MB tumors, thereby paving the way for more targeted and less toxic therapeutic strategies. Full article

(This article belongs to the Special Issue Brain Tumors Treatment: Current and Future Challenges from Drug Formulations to Delivery Methods)

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14 pages, 1225 KiB

Open AccessEditor’s ChoiceReview

Beyond Traditional Sunscreens: A Review of Liposomal-Based Systems for Photoprotection

by Júlio Abreu Miranda, Yasmin Ferreira da Cruz, Ícaro Chaves Girão, Fabia Julliana Jorge de Souza, Wógenes Nunes de Oliveira, Éverton do Nascimento Alencar, Lucas Amaral-Machado and Eryvaldo Sócrates Tabosa do Egito

Pharmaceutics 2024, 16(5), 661; https://doi.org/10.3390/pharmaceutics16050661 - 15 May 2024

Viewed by 755

Abstract

Sunscreen products are essential for shielding the skin from ultraviolet (UV) radiation, a leading cause of skin cancer. While existing products serve this purpose, there is a growing need to enhance their efficacy while minimizing potential systemic absorption of UV filters and associated [...] Read more.

Sunscreen products are essential for shielding the skin from ultraviolet (UV) radiation, a leading cause of skin cancer. While existing products serve this purpose, there is a growing need to enhance their efficacy while minimizing potential systemic absorption of UV filters and associated toxicological risks. Liposomal-based formulations have emerged as a promising approach to address these challenges and develop advanced photoprotective products. These vesicular systems offer versatility in carrying both hydrophilic and lipophilic UV filters, enabling the creation of broad-spectrum sunscreens. Moreover, their composition based on phospholipids, resembling that of the stratum corneum, facilitates adherence to the skin’s surface layers, thereby improving photoprotective efficacy. The research discussed in this review underscores the significant advantages of liposomes in photoprotection, including their ability to limit the systemic absorption of UV filters, enhance formulation stability, and augment photoprotective effects. However, despite these benefits, there remains a notable gap between the potential of liposomal systems and their utilization in sunscreen development. Consequently, this review emphasizes the importance of leveraging liposomes and related vesicular systems as innovative tools for crafting novel and more efficient photoprotective formulations. Full article

(This article belongs to the Special Issue Nano-Based Drug Delivery System: Recent Developments and Future Prospects)

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23 pages, 11650 KiB

Open AccessEditor’s ChoiceArticle

Sweeteners Show a Plasticizing Effect on PVP K30—A Solution for the Hot-Melt Extrusion of Fixed-Dose Amorphous Curcumin-Hesperetin Solid Dispersions

by Kamil Wdowiak, Lidia Tajber, Andrzej Miklaszewski and Judyta Cielecka-Piontek

Pharmaceutics 2024, 16(5), 659; https://doi.org/10.3390/pharmaceutics16050659 - 15 May 2024

Viewed by 676

Abstract

The co-administration of curcumin and hesperetin might be beneficial in terms of neuroprotective activity; therefore, in this study, we attempted to develop a fixed-dose formulation comprising these two compounds in an amorphous state. The aim of obtaining an amorphous state was to overcome [...] Read more.

The co-administration of curcumin and hesperetin might be beneficial in terms of neuroprotective activity; therefore, in this study, we attempted to develop a fixed-dose formulation comprising these two compounds in an amorphous state. The aim of obtaining an amorphous state was to overcome the limitations of the low solubility of the active compounds. First, we assessed the possibility of using popular sweeteners (erythritol, xylitol, and sorbitol) as plasticizers to reduce the glass transition temperature of PVP K30 to prepare the polymer–excipient blends, which allowed the preparation of amorphous solid dispersions via hot-melt extrusion at a temperature below the original glass transition of PVP K30. Erythritol proved to be the superior plasticizer. Then, we focused on the development of fixed-dose amorphous solid dispersions of curcumin and hesperetin. Powder X-ray diffraction and thermal analysis confirmed the amorphous character of dispersions, whereas infrared spectroscopy helped to assess the presence of intermolecular interactions. The amorphous state of the produced dispersions was maintained for 6 months, as shown in a stability study. Pharmaceutical parameters such as dissolution rate, solubility, and in vitro permeability through artificial membranes were evaluated. The best improvement in these features was noted for the dispersion, which contained 15% of the total content of the active compounds with erythritol used as the plasticizer. Full article

(This article belongs to the Special Issue Further Research in Polyphenols Formulations)

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20 pages, 3609 KiB

Open AccessEditor’s ChoiceArticle

An Investigation into the Effects of Processing Factors on the Properties and Scaling-Up Potential of Propranolol-Loaded Chitosan Nanogels

by Hei Ming Kenneth Ho, Richard M. Day and Duncan Q. M. Craig

Pharmaceutics 2024, 16(5), 662; https://doi.org/10.3390/pharmaceutics16050662 - 15 May 2024

Viewed by 526

Abstract

Chitosan-triphosphate (TPP) nanogels are widely studied drug delivery carrier systems, typically prepared via a simple mixing process. However, the effects of the processing factors on nanogel production have not been extensively explored, despite the importance of understanding and standardising such factors to allow [...] Read more.

Chitosan-triphosphate (TPP) nanogels are widely studied drug delivery carrier systems, typically prepared via a simple mixing process. However, the effects of the processing factors on nanogel production have not been extensively explored, despite the importance of understanding and standardising such factors to allow upscaling and commercial usage. This study aims to systematically evaluate the effects of various fabrication and processing factors on the properties of nanogels using a Design of Experiment approach. Hydrodynamic size, polydispersity index (PDI), zeta potential, and encapsulation efficiency were determined as the dependent factors. The temperature, stirring rate, chitosan grade, crosslinker choice, and the interaction term between temperature and chitosan grade were found to have a significant effect on the particle size, whereas the effect of temperature and the addition rate of crosslinker on the PDI was also noteworthy. Moreover, the addition rate of the crosslinker and the volume of the reaction vessel were found to impact the encapsulation efficiency. The zeta potential of the nanogels was found to be governed by the chitosan grade. The optimal fabrication conditions for the development of medium molecular weight chitosan and TPP nanogels included the following: the addition rate for TPP solution was set at 2 mL/min, while the solution was then stirred at a temperature of 50 °C and a stirring speed of 600 rpm. The volume of the glass vial used was 28 mL, while the stirrer size was 20 mm. The second aim of the study was to evaluate the potential for scaling up the nanogels. Size and PDI were found to increase from 128 nm to 151 nm and from 0.232 to 0.267, respectively, when the volume of the reaction mixture was increased from 4 to 20 mL and other processing factors were kept unchanged. These results indicate that caution is required when scaling up as the nanogel properties may be significantly altered with an increasing production scale. Full article

(This article belongs to the Section Nanomedicine and Nanotechnology)

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24 pages, 5816 KiB

Open AccessEditor’s ChoiceReview

Functionalized Calcium Carbonate-Based Microparticles as a Versatile Tool for Targeted Drug Delivery and Cancer Treatment

by Lara Biny, Evgeniia Gerasimovich, Alexander Karaulov, Alyona Sukhanova and Igor Nabiev

Pharmaceutics 2024, 16(5), 653; https://doi.org/10.3390/pharmaceutics16050653 - 13 May 2024

Viewed by 879

Abstract

Nano- and microparticles are increasingly widely used in biomedical research and applications, particularly as specific labels and targeted delivery vehicles. Silica has long been considered the best material for such vehicles, but it has some disadvantages limiting its potential, such as the proneness [...] Read more.

Nano- and microparticles are increasingly widely used in biomedical research and applications, particularly as specific labels and targeted delivery vehicles. Silica has long been considered the best material for such vehicles, but it has some disadvantages limiting its potential, such as the proneness of silica-based carriers to spontaneous drug release. Calcium carbonate (CaCO₃) is an emerging alternative, being an easily available, cost-effective, and biocompatible material with high porosity and surface reactivity, which makes it an attractive choice for targeted drug delivery. CaCO₃ particles are used in this field in the form of either bare CaCO₃ microbeads or core/shell microparticles representing polymer-coated CaCO₃ cores. In addition, they serve as removable templates for obtaining hollow polymer microcapsules. Each of these types of particles has its specific advantages in terms of biomedical applications. CaCO₃ microbeads are primarily used due to their capacity for carrying pharmaceutics, whereas core/shell systems ensure better protection of the drug-loaded core from the environment. Hollow polymer capsules are particularly attractive because they can encapsulate large amounts of pharmaceutical agents and can be so designed as to release their contents in the target site in response to specific stimuli. This review focuses first on the chemistry of the CaCO₃ cores, core/shell microbeads, and polymer microcapsules. Then, systems using these structures for the delivery of therapeutic agents, including drugs, proteins, and DNA, are outlined. The results of the systematic analysis of available data are presented. They show that the encapsulation of various therapeutic agents in CaCO₃-based microbeads or polymer microcapsules is a promising technique of drug delivery, especially in cancer therapy, enhancing drug bioavailability and specific targeting of cancer cells while reducing side effects. To date, research in CaCO₃-based microparticles and polymer microcapsules assembled on CaCO₃ templates has mainly dealt with their properties in vitro, whereas their in vivo behavior still remains poorly studied. However, the enormous potential of these highly biocompatible carriers for in vivo applications is undoubted. This last issue is addressed in depth in the Conclusions and Outlook sections of the review. Full article

(This article belongs to the Topic Recent Advances in Anticancer Strategies)

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23 pages, 4276 KiB

Open AccessEditor’s ChoiceArticle

Drug Integrating Amphiphilic Nano-Assemblies: 2. Spatiotemporal Distribution within Inflammation Sites

by Teresa De Toni, Teodora Dal Buono, Chris M. Li, Grisell C. Gonzalez, Sung-Ting Chuang, Peter Buchwald, Alice A. Tomei and Diana Velluto

Pharmaceutics 2024, 16(5), 652; https://doi.org/10.3390/pharmaceutics16050652 - 13 May 2024

Viewed by 760

Abstract

The need for chronic systemic immunosuppression, which is associated with unavoidable side-effects, greatly limits the applicability of allogeneic cell transplantation for regenerative medicine applications including pancreatic islet cell transplantation to restore insulin production in type 1 diabetes (T1D). Cell transplantation in confined sites [...] Read more.

The need for chronic systemic immunosuppression, which is associated with unavoidable side-effects, greatly limits the applicability of allogeneic cell transplantation for regenerative medicine applications including pancreatic islet cell transplantation to restore insulin production in type 1 diabetes (T1D). Cell transplantation in confined sites enables the localized delivery of anti-inflammatory and immunomodulatory drugs to prevent graft loss by innate and adaptive immunity, providing an opportunity to achieve local effects while minimizing unwanted systemic side effects. Nanoparticles can provide the means to achieve the needed localized and sustained drug delivery either by graft targeting or co-implantation. Here, we evaluated the potential of our versatile platform of drug-integrating amphiphilic nanomaterial assemblies (DIANAs) for targeted drug delivery to an inflamed site model relevant for islet transplantation. We tested either passive targeting of intravenous administered spherical nanomicelles (nMIC; 20–25 nm diameter) or co-implantation of elongated nanofibrils (nFIB; 5 nm diameter and >1 μm length). To assess the ability of nMIC and nFIB to target an inflamed graft site, we used a lipophilic fluorescent cargo (DiD and DiR) and evaluated the in vivo biodistribution and cellular uptake in the graft site and other organs, including draining and non-draining lymph nodes, after systemic administration (nMIC) and/or graft co-transplantation (nFIB) in mice. Localized inflammation was generated either by using an LPS injection or by using biomaterial-coated islet-like bead implantation in the subcutaneous site. A cell transplant inflammation model was used as well to test nMIC- and nFIB-targeted biodistribution. We found that nMIC can reach the inflamed site after systemic administration, while nFIB remains localized for several days after co-implantation. We confirmed that DIANAs are taken up by different immune cell populations responsible for graft inflammation. Therefore, DIANA is a useful approach for targeted and/or localized delivery of immunomodulatory drugs to decrease innate and adaptive immune responses that cause graft loss after transplantation of therapeutic cells. Full article

(This article belongs to the Special Issue Self-Assembled Amphiphilic Copolymers in Drug Delivery, 2nd Edition)

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30 pages, 3155 KiB

Open AccessEditor’s ChoiceReview

Ciprofloxacin-Loaded Inhalable Formulations against Lower Respiratory Tract Infections: Challenges, Recent Advances, and Future Perspectives

by Vijay Kumar Panthi, Kathryn E. Fairfull-Smith and Nazrul Islam

Pharmaceutics 2024, 16(5), 648; https://doi.org/10.3390/pharmaceutics16050648 - 11 May 2024

Viewed by 1646

Abstract

Inhaled ciprofloxacin (CFX) has been investigated as a treatment for lower respiratory tract infections (LRTIs) associated with cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), and bronchiectasis. The challenges in CFX effectiveness for LRTI treatment include poor aqueous solubility and therapy resistance. CFX [...] Read more.

Inhaled ciprofloxacin (CFX) has been investigated as a treatment for lower respiratory tract infections (LRTIs) associated with cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), and bronchiectasis. The challenges in CFX effectiveness for LRTI treatment include poor aqueous solubility and therapy resistance. CFX dry powder for inhalation (DPI) formulations were well-tolerated, showing a remarkable decline in overall bacterial burden compared to a placebo in bronchiectasis patients. Recent research using an inhalable powder combining Pseudomonas phage PEV20 with CFX exhibited a substantial reduction in bacterial density in mouse lungs infected with clinical P. aeruginosa strains and reduced inflammation. Currently, studies suggest that elevated biosynthesis of fatty acids could serve as a potential biomarker for detecting CFX resistance in LRTIs. Furthermore, inhaled CFX has successfully addressed various challenges associated with traditional CFX, including the incapacity to eliminate the pathogen, the recurrence of colonization, and the development of resistance. However, further exploration is needed to address three key unresolved issues: identifying the right patient group, determining the optimal treatment duration, and accurately assessing the risk of antibiotic resistance, with additional multicenter randomized controlled trials suggested to tackle these challenges. Importantly, future investigations will focus on the effectiveness of CFX DPI in bronchiectasis and COPD, aiming to differentiate prognoses between these two conditions. This review underscores the importance of CFX inhalable formulations against LRTIs in preclinical and clinical sectors, their challenges, recent advancements, and future perspectives. Full article

(This article belongs to the Special Issue Recent Advances in Pulmonary Drug Delivery Systems)

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37 pages, 10656 KiB

Open AccessEditor’s ChoiceArticle

Synthesis, Characterisation, and In Vitro Evaluation of Biocompatibility, Antibacterial and Antitumor Activity of Imidazolium Ionic Liquids

by Elisabetta Novello, Giuseppina Scalzo, Giovanni D’Agata, Maria G. Raucci, Luigi Ambrosio, Alessandra Soriente, Barbara Tomasello, Cristina Restuccia, Lucia Parafati, Grazia M. L. Consoli, Loredana Ferreri, Antonio Rescifina, Chiara Zagni and Daniela C. Zampino

Pharmaceutics 2024, 16(5), 642; https://doi.org/10.3390/pharmaceutics16050642 - 10 May 2024

Viewed by 944

Abstract

In recent decades, ionic liquids (ILs) have garnered research interest for their noteworthy properties, such as thermal stability, low or no flammability, and negligible vapour pressure. Moreover, their tunability offers limitless opportunities to design ILs with properties suitable for applications in many industrial [...] Read more.

In recent decades, ionic liquids (ILs) have garnered research interest for their noteworthy properties, such as thermal stability, low or no flammability, and negligible vapour pressure. Moreover, their tunability offers limitless opportunities to design ILs with properties suitable for applications in many industrial fields. This study aims to synthetise two series of methylimidazolium ILs bearing long alkyl chain in their cations (C9, C10, C12, C14, C16, C18, C20) and with tetrafluoroborate (BF₄) and the 1,3-dimethyl-5-sulfoisophthalate (DMSIP) as counter ions. The ILs were characterised using ¹H-NMR and MALDI-TOF, and their thermal behaviour was investigated through DSC and TGA. Additionally, the antimicrobial, anticancer, and cytotoxic activities of the ILs were analysed. Moreover, the most promising ILs were incorporated at different concentrations (0.5, 1, 5 wt%) into polyvinyl chloride (PVC) by solvent casting to obtain antimicrobial blend films. The thermal properties and stability of the resulting PVC/IL films, along with their hydrophobicity/hydrophilicity, IL surface distribution, and release, were studied using DSC and TGA, contact angle (CA), SEM, and UV–vis spectrometry, respectively. Furthermore, the antimicrobial and cytotoxic properties of blends were analysed. The in vitro results demonstrated that the antimicrobial and antitumor activities of pure ILs against t Listeria monocytogenes, Escherichia coli, Pseudomonas fluorescens strains, and the breast cancer cell line (MCF7), respectively, were mainly dependent on their structure. These activities were higher in the series containing the BF₄ anion and increased with the increase in the methylimidazolium cation alkyl chain length. However, the elongation of the alkyl chain beyond C16 induced a decrease in antimicrobial activity, indicating a cut-off effect. A similar trend was also observed in terms of in vitro biocompatibility. The loading of both the series of ILs into the PVC matrix did not affect the thermal stability of PVC blend films. However, their T_onset decreased with increased IL concentration and alkyl chain length. Similarly, both the series of PVC/IL films became more hydrophilic with increasing IL concentration and alkyl chain. The loading of ILs at 5% concentration led to considerable IL accumulation on the blend film surfaces (as observed in SEM images) and, subsequently, their higher release. The biocompatibility assessment with healthy human dermal fibroblast (HDF) cells and the investigation of antitumoral properties unveiled promising pharmacological characteristics. These findings provide strong support for the potential utilisation of ILs in biomedical applications, especially in the context of cancer therapy and as antibacterial agents to address the challenge of antibiotic resistance. Furthermore, the unique properties of the PVC/IL films make them versatile materials for advancing healthcare technologies, from drug delivery to tissue engineering and antimicrobial coatings to diagnostic devices. Full article

(This article belongs to the Special Issue Ionic Liquids in Pharmaceutical and Biomedical Applications, 2nd Edition)

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22 pages, 5833 KiB

Open AccessEditor’s ChoiceArticle

A Novel Approach for Dermal Application of Pranoprofen-Loaded Lipid Nanoparticles for the Treatment of Post-Tattoo Inflammatory Reactions

by Guillermo De Grau-Bassal, Mireia Mallandrich, Lilian Sosa, Lupe Espinoza, Ana Cristina Calpena, Núria Bozal-de Febrer, María J. Rodríguez-Lagunas, María L. Garduño-Ramírez and María Rincón

Pharmaceutics 2024, 16(5), 643; https://doi.org/10.3390/pharmaceutics16050643 - 10 May 2024

Cited by 1 | Viewed by 1137

Abstract

Recently, the number of people acquiring tattoos has increased, with tattoos gaining significant popularity in people between 20 and 40 years old. Inflammation is a common reaction associated with tattooing. The purpose of this study was to evaluate a nanostructured lipid carrier loading [...] Read more.

Recently, the number of people acquiring tattoos has increased, with tattoos gaining significant popularity in people between 20 and 40 years old. Inflammation is a common reaction associated with tattooing. The purpose of this study was to evaluate a nanostructured lipid carrier loading pranoprofen (PRA-NLC) as a tattoo aftercare formulation to reduce the inflammation associated with tattooing. In this context, the in vitro drug release and the ex vivo permeation-through-human-skin tests using Franz cells were appraised. The tolerance of our formulation on the skin was evaluated by studying the skin’s biomechanical properties. In addition, an in vivo anti-inflammatory study was conducted on mice skin to evaluate the efficacy of the formulation applied topically after tattooing the animals. PRA-NLC showed a sustained release up to 72 h, and the amount of pranoprofen retained in the skin was found to be 33.48 µg/g/cm². The formulation proved to be well tolerated; it increased stratum corneum hydration, and no signs of skin irritation were observed. Furthermore, it was demonstrated to be non-cytotoxic since the cell viability was greater than 80%. Based on these results, we concluded that PRA-NLC represents a suitable drug delivery carrier for the transdermal delivery of pranoprofen to alleviate the local skin inflammation associated with tattooing. Full article

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31 pages, 1659 KiB

Open AccessEditor’s ChoiceReview

Lipid Nanoparticles in Lung Cancer Therapy

by Hossein Omidian, Erma J. Gill and Luigi X. Cubeddu

Pharmaceutics 2024, 16(5), 644; https://doi.org/10.3390/pharmaceutics16050644 - 10 May 2024

Viewed by 865

Abstract

This manuscript explores the use of lipid nanoparticles (LNPs) in addressing the pivotal challenges of lung cancer treatment, including drug delivery inefficacy and multi-drug resistance. LNPs have significantly advanced targeted therapy by improving the precision and reducing the systemic toxicity of chemotherapeutics such [...] Read more.

This manuscript explores the use of lipid nanoparticles (LNPs) in addressing the pivotal challenges of lung cancer treatment, including drug delivery inefficacy and multi-drug resistance. LNPs have significantly advanced targeted therapy by improving the precision and reducing the systemic toxicity of chemotherapeutics such as doxorubicin and paclitaxel. This manuscript details the design and benefits of various LNP systems, including solid lipid–polymer hybrids, which offer controlled release and enhanced drug encapsulation. Despite achievements in reducing tumor size and enhancing survival, challenges such as manufacturing complexity, biocompatibility, and variable clinical outcomes persist. Future directions are aimed at refining targeting capabilities, expanding combinatorial therapies, and integrating advanced manufacturing techniques to tailor treatments to individual patient profiles, thus promising to transform lung cancer therapy through interdisciplinary collaboration and regulatory innovation. Full article

(This article belongs to the Special Issue Lipid Nanostructures as Drug Carriers for Cancer Therapy)

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13 pages, 1303 KiB

Open AccessEditor’s ChoiceArticle

Effect of Antioxidants in Medicinal Products on Intestinal Drug Transporters

by Chetan P. Kulkarni, Jia Yang, Megan L. Koleske, Giovanni Lara, Khondoker Alam, Andre Raw, Bhagwant Rege, Liang Zhao, Dongmei Lu, Lei Zhang, Lawrence X. Yu, Robert A. Lionberger, Kathleen M. Giacomini, Deanna L. Kroetz and Sook Wah Yee

Pharmaceutics 2024, 16(5), 647; https://doi.org/10.3390/pharmaceutics16050647 - 10 May 2024

Cited by 1 | Viewed by 985

Abstract

The presence of mutagenic and carcinogenic N-nitrosamine impurities in medicinal products poses a safety risk. While incorporating antioxidants in formulations is a potential mitigation strategy, concerns arise regarding their interference with drug absorption by inhibiting intestinal drug transporters. Our study screened thirty antioxidants [...] Read more.

The presence of mutagenic and carcinogenic N-nitrosamine impurities in medicinal products poses a safety risk. While incorporating antioxidants in formulations is a potential mitigation strategy, concerns arise regarding their interference with drug absorption by inhibiting intestinal drug transporters. Our study screened thirty antioxidants for inhibitory effects on key intestinal transporters—OATP2B1, P-gp, and BCRP in HEK-293 cells (OATP2B1) or membrane vesicles (P-gp, BCRP) using ³H-estrone sulfate, ³H-N-methyl quinidine, and ³H-CCK8 as substrates, respectively. The screen identified that butylated hydroxyanisole (BHA) and carnosic acid inhibited all three transporters (OATP2B1, P-gp, and BCRP), while ascorbyl palmitate (AP) inhibited OATP2B1 by more than 50%. BHA had IC₅₀ values of 71 ± 20 µM, 206 ± 14 µM, and 182 ± 49 µM for OATP2B1, BCRP, and P-gp, respectively. AP exhibited IC₅₀ values of 23 ± 10 µM for OATP2B1. The potency of AP and BHA was tested with valsartan, an OATP2B1 substrate, and revealed IC₅₀ values of 26 ± 17 µM and 19 ± 11 µM, respectively, in HEK-293-OATP2B1 cells. Comparing IC₅₀ values of AP and BHA with estimated intestinal concentrations suggests an unlikely inhibition of intestinal transporters at clinical concentrations of drugs formulated with antioxidants. Full article

(This article belongs to the Special Issue New Insights into Transporters in Drug Development)

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22 pages, 1808 KiB

Open AccessEditor’s ChoiceReview

Innovative Delivery Systems for Curcumin: Exploring Nanosized and Conventional Formulations

by Jibira Yakubu and Amit V. Pandey

Pharmaceutics 2024, 16(5), 637; https://doi.org/10.3390/pharmaceutics16050637 - 9 May 2024

Viewed by 1082

Abstract

Curcumin, a polyphenol with a rich history spanning two centuries, has emerged as a promising therapeutic agent targeting multiple signaling pathways and exhibiting cellular-level activities that contribute to its diverse health benefits. Extensive preclinical and clinical studies have demonstrated its ability to enhance [...] Read more.

Curcumin, a polyphenol with a rich history spanning two centuries, has emerged as a promising therapeutic agent targeting multiple signaling pathways and exhibiting cellular-level activities that contribute to its diverse health benefits. Extensive preclinical and clinical studies have demonstrated its ability to enhance the therapeutic potential of various bioactive compounds. While its reported therapeutic advantages are manifold, predominantly attributed to its antioxidant and anti-inflammatory properties, its efficacy is hindered by poor bioavailability stemming from inadequate absorption, rapid metabolism, and elimination. To address this challenge, nanodelivery systems have emerged as a promising approach, offering enhanced solubility, biocompatibility, and therapeutic effects for curcumin. We have analyzed the knowledge on curcumin nanoencapsulation and its synergistic effects with other compounds, extracted from electronic databases. We discuss the pharmacokinetic profile of curcumin, current advancements in nanoencapsulation techniques, and the combined effects of curcumin with other agents across various disorders. By unifying existing knowledge, this analysis intends to provide insights into the potential of nanoencapsulation technologies to overcome constraints associated with curcumin treatments, emphasizing the importance of combinatorial approaches in improving therapeutic efficacy. Finally, this compilation of study data aims to inform and inspire future research into encapsulating drugs with poor pharmacokinetic characteristics and investigating innovative drug combinations to improve bioavailability and therapeutic outcomes. Full article

(This article belongs to the Special Issue Curcumin in Biomedical Applications, 2nd Edition)

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18 pages, 1370 KiB

Open AccessEditor’s ChoiceReview

An Overview of Hydrothermally Synthesized Titanate Nanotubes: The Factors Affecting Preparation and Their Promising Pharmaceutical Applications

by Ranim Saker, Hadi Shammout, Géza Regdon, Jr. and Tamás Sovány

Pharmaceutics 2024, 16(5), 635; https://doi.org/10.3390/pharmaceutics16050635 - 9 May 2024

Viewed by 697

Abstract

Recently, titanate nanotubes (TNTs) have been receiving more attention and becoming an attractive candidate for use in several disciplines. With their promising results and outstanding performance, they bring added value to any field using them, such as green chemistry, engineering, and medicine. Their [...] Read more.

Recently, titanate nanotubes (TNTs) have been receiving more attention and becoming an attractive candidate for use in several disciplines. With their promising results and outstanding performance, they bring added value to any field using them, such as green chemistry, engineering, and medicine. Their good biocompatibility, high resistance, and special physicochemical properties also provide a wide spectrum of advantages that could be of crucial importance for investment in different platforms, especially medical and pharmaceutical ones. Hydrothermal treatment is one of the most popular methods for TNT preparation because it is a simple, cost-effective, and environmentally friendly water-based procedure. It is also considered as a strong candidate for large-scale production intended for biomedical application because of its high yield and the special properties of the resulting nanotubes, especially their small diameters, which are more appropriate for drug delivery and long circulation. TNTs’ properties highly differ according to the preparation conditions, which would later affect their subsequent application field. The aim of this review is to discuss the factors that could possibly affect their synthesis and determine the transformations that could happen according to the variation of factors. To fulfil this aim, relevant scientific databases (Web of Science, Scopus, PubMed, etc.) were searched using the keywords titanate nanotubes, hydrothermal treatment, synthesis, temperature, time, alkaline medium, post treatment, acid washing, calcination, pharmaceutical applications, drug delivery, etc. The articles discussing TNTs preparation by hydrothermal synthesis were selected, and papers discussing other preparation methods were excluded; then, the results were evaluated based on a careful reading of the selected articles. This investigation and comprehensive review of different parameters could be the answer to several problems concerning establishing a producible method of TNTs production, and it might also help to optimize their characteristics and then extend their application limits to further domains that are not yet totally revealed, especially the pharmaceutical industry and drug delivery. Full article

(This article belongs to the Special Issue Advanced Pharmaceutical Excipients Used in Solid Dosage Forms)

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19 pages, 2319 KiB

Open AccessEditor’s ChoiceReview

The Potential of Selenium-Based Therapies for Ocular Oxidative Stress

by Lulwah Al-Bassam, Gemma C. Shearman, Steve Brocchini, Raid G. Alany and Gareth R. Williams

Pharmaceutics 2024, 16(5), 631; https://doi.org/10.3390/pharmaceutics16050631 - 8 May 2024

Viewed by 847

Abstract

Oxidative stress plays a critical role in the development of chronic ocular conditions including cataracts, age-related macular degeneration, and diabetic retinopathy. There is a need to explore the potential of topical antioxidants to slow the progression of those conditions by mediating oxidative stress [...] Read more.

Oxidative stress plays a critical role in the development of chronic ocular conditions including cataracts, age-related macular degeneration, and diabetic retinopathy. There is a need to explore the potential of topical antioxidants to slow the progression of those conditions by mediating oxidative stress and maintaining ocular health. Selenium has attracted considerable attention because it is a component of selenoproteins and antioxidant enzymes. The application of selenium to a patient can increase selenoprotein expression, counteracting the effect of reactive oxygen species by increasing the presence of antioxidant enzymes, and thus slowing the progression of chronic ocular disorders. Oxidative stress effects at the biomolecular level for prevalent ocular conditions are described in this review along with some of the known defensive mechanisms, with a focus on selenoproteins. The importance of selenium in the eye is described, along with a discussion of selenium studies and uses. Selenium’s antioxidant and anti-inflammatory qualities may prevent or delay eye diseases. Recent breakthroughs in drug delivery methods and nanotechnology for selenium-based ocular medication delivery are enumerated. Different types of selenium may be employed in formulations aimed at managing ocular oxidative stress conditions. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation: Novel Drug Formulation and Delivery Systems)

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17 pages, 17237 KiB

Open AccessEditor’s ChoiceArticle

Using Polymers as Crystal Inhibitors to Prevent the Crystallization of the Rotigotine Patch

by Qiantong Liu, Xing Li, Bo Liu, Jiahao Kong, Qing Wang and Zhigang Gao

Pharmaceutics 2024, 16(5), 630; https://doi.org/10.3390/pharmaceutics16050630 - 8 May 2024

Viewed by 673

Abstract

This study aimed to enhance the stability of the Rotigotine (ROT) patch using polymers as crystal inhibitors. Three polymers (Poloxamer 188, Soluplus, TPGS) were selected as crystal inhibitors to formulate ROT patches with varying drug loadings (20%, 40%, 60%, and 80%, w/ [...] Read more.

This study aimed to enhance the stability of the Rotigotine (ROT) patch using polymers as crystal inhibitors. Three polymers (Poloxamer 188, Soluplus, TPGS) were selected as crystal inhibitors to formulate ROT patches with varying drug loadings (20%, 40%, 60%, and 80%, w/w). SEM and XRD analysis revealed that the Soluplus and Soluplus-TPGS groups with a high concentration (80%, w/w) of ROT could be stored at room temperature for at least 90 days without crystallization. Moreover, the crystallization nucleation time and growth rate were utilized to assess the ability of Poloxamer 188, Soluplus, and TPGS to hinder the formation of ROT crystals and slow down its crystallization rate. Molecular docking results elucidated the intermolecular forces between ROT and different polymers, revealing their mechanisms for crystal inhibition. The ROT-Soluplus-TPGS combination exhibited the lowest binding free energy (−5.3 kcal/mol), indicating the highest binding stability, thereby effectively reducing crystal precipitation. In vitro skin permeation studies demonstrated that ROT patches containing crystal inhibitors exhibited promising transdermal effects. With increasing ROT concentration, the cumulative drug permeation substantially increased, while the lag time was notably reduced. This study offers novel insights for the development of ROT patches. Full article

(This article belongs to the Special Issue Formulation of Poorly Water-Soluble Drugs)

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17 pages, 3262 KiB

Open AccessEditor’s ChoiceArticle

Five Novel Polymorphs of Cardarine/GW501516 and Their Characterization by X-ray Diffraction, Computational Methods, Thermal Analysis and a Pharmaceutical Perspective

by Alexandru Turza, Petru Pascuta, Marieta Muresan-Pop, Liviu Mare, Gheorghe Borodi and Violeta Popescu

Pharmaceutics 2024, 16(5), 623; https://doi.org/10.3390/pharmaceutics16050623 - 7 May 2024

Viewed by 880

Abstract

GW501516, also known by the name of cardarine, is a synthetic peroxisome-proliferator-activated receptor delta (PPR-δ) agonist agent developed for applications in the treatment of metabolic disorders and cardiovascular diseases. A broad polymorph screening in various solvents and mixtures was completed in order to [...] Read more.

GW501516, also known by the name of cardarine, is a synthetic peroxisome-proliferator-activated receptor delta (PPR-δ) agonist agent developed for applications in the treatment of metabolic disorders and cardiovascular diseases. A broad polymorph screening in various solvents and mixtures was completed in order to explore its capabilities to grow polymorphs. The crystal structures of four polymorphs were elucidated using single-crystal X-ray diffraction, while one structure was solved via a powder X-ray diffraction method. The solid state features (nature of intermolecular interactions) were investigated by computational methods. The polymorphs were further investigated by thermal DSC analysis and X-ray diffraction on powders. From a pharmaceutical perspective, the stability and solubility of the polymorphs were analyzed as well. Full article

(This article belongs to the Special Issue Pharmaceutical Polymorphs and Cocrystals and Their In Vitro and In Vivo Evaluation)

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24 pages, 3539 KiB

Open AccessEditor’s ChoiceReview

Challenges in Optimizing Nanoplatforms Used for Local and Systemic Delivery in the Oral Cavity

by Dorin Ioan Cocoș, Olimpia Dumitriu Buzia, Alin Laurențiu Tatu, Monica Dinu, Lawrence Chukwudi Nwabudike, Claudia Simona Stefan, Kamel Earar and Carmen Galea

Pharmaceutics 2024, 16(5), 626; https://doi.org/10.3390/pharmaceutics16050626 - 7 May 2024

Viewed by 870

Abstract

In this study, we focused on innovative approaches to improve drug administration in oral pathology, especially by transmucosal and transdermal pathways. These improvements refer to the type of microneedles used (proposing needles in the saw), to the use of certain enhancers such as [...] Read more.

In this study, we focused on innovative approaches to improve drug administration in oral pathology, especially by transmucosal and transdermal pathways. These improvements refer to the type of microneedles used (proposing needles in the saw), to the use of certain enhancers such as essential oils (which, besides the amplifier action, also have intrinsic actions on oral health), to associations of active substances with synergistic action, as well as the use of copolymeric membranes, cemented directly on the tooth. We also propose a review of the principles of release at the level of the oral mucosa and of the main release systems used in oral pathology. Controlled failure systems applicable in oral pathology include the following: fast dissolving films, mucoadhesive tablets, hydrogels, intraoral mucoadhesive films, composite wafers, and smart drugs. The novelty elements brought by this paper refer to the possibilities of optimizing the localized drug delivery system in osteoarthritis of the temporomandibular joint, neuropathic pain, oral cancer, periodontitis, and pericoronitis, as well as in maintaining oral health. We would like to mention the possibility of incorporating natural products into the controlled failure systems used in oral pathology, paying special attention to essential oils. Full article

(This article belongs to the Section Drug Delivery and Controlled Release)

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14 pages, 1529 KiB

Open AccessEditor’s ChoiceArticle

Enhancing Cellular Uptake of Native Proteins through Bio-Orthogonal Conjugation with Chemically Synthesized Cell-Penetrating Peptides

by Jekaterina Nebogatova, Ly Porosk, Heleri Heike Härk and Kaido Kurrikoff

Pharmaceutics 2024, 16(5), 617; https://doi.org/10.3390/pharmaceutics16050617 - 3 May 2024

Cited by 1 | Viewed by 886

Abstract

The potential for native proteins to serve as a platform for biocompatible, targeted, and personalized therapeutics in the context of genetic and metabolic disorders is vast. Nevertheless, their clinical application encounters challenges, particularly in overcoming biological barriers and addressing the complexities involved in [...] Read more.

The potential for native proteins to serve as a platform for biocompatible, targeted, and personalized therapeutics in the context of genetic and metabolic disorders is vast. Nevertheless, their clinical application encounters challenges, particularly in overcoming biological barriers and addressing the complexities involved in engineering transmembrane permeability. This study is dedicated to the development of a multifunctional nanoentity in which a model therapeutic protein is covalently linked to a cell-penetrating peptide, NickFect 55, with the objective of enhancing its intracellular delivery. Successful binding of the nanoentity fragments was achieved through the utilization of an intein-mediated protein-trans splicing reaction. Our research demonstrates that the fully assembled nanoentity-containing protein was effectively internalized by the cells, underscoring the potential of this approach in overcoming barriers associated with protein-based therapeutics for the treatment of genetic disorders. Full article

(This article belongs to the Special Issue Delivery System for Biomacromolecule Drugs: Design and Application)

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20 pages, 2199 KiB

Open AccessEditor’s ChoiceArticle

Organ-on-a-Chip: Ubi sumus? Fundamentals and Design Aspects

by Ana Sofia Morais, Maria Mendes, Marta Agostinho Cordeiro, João J. Sousa, Alberto Canelas Pais, Silvia M. Mihăilă and Carla Vitorino

Pharmaceutics 2024, 16(5), 615; https://doi.org/10.3390/pharmaceutics16050615 - 2 May 2024

Viewed by 957

Abstract

This review outlines the evolutionary journey from traditional two-dimensional (2D) cell culture to the revolutionary field of organ-on-a-chip technology. Organ-on-a-chip technology integrates microfluidic systems to mimic the complex physiological environments of human organs, surpassing the limitations of conventional 2D cultures. This evolution has [...] Read more.

This review outlines the evolutionary journey from traditional two-dimensional (2D) cell culture to the revolutionary field of organ-on-a-chip technology. Organ-on-a-chip technology integrates microfluidic systems to mimic the complex physiological environments of human organs, surpassing the limitations of conventional 2D cultures. This evolution has opened new possibilities for understanding cell–cell interactions, cellular responses, drug screening, and disease modeling. However, the design and manufacture of microchips significantly influence their functionality, reliability, and applicability to different biomedical applications. Therefore, it is important to carefully consider design parameters, including the number of channels (single, double, or multi-channels), the channel shape, and the biological context. Simultaneously, the selection of appropriate materials compatible with the cells and fabrication methods optimize the chips’ capabilities for specific applications, mitigating some disadvantages associated with these systems. Furthermore, the success of organ-on-a-chip platforms greatly depends on the careful selection and utilization of cell resources. Advances in stem cell technology and tissue engineering have contributed to the availability of diverse cell sources, facilitating the development of more accurate and reliable organ-on-a-chip models. In conclusion, a holistic perspective of in vitro cellular modeling is provided, highlighting the integration of microfluidic technology and meticulous chip design, which play a pivotal role in replicating organ-specific microenvironments. At the same time, the sensible use of cell resources ensures the fidelity and applicability of these innovative platforms in several biomedical applications. Full article

(This article belongs to the Section Pharmaceutical Technology, Manufacturing and Devices)

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13 pages, 1154 KiB

Open AccessEditor’s ChoiceArticle

The Role of a Cholecystokinin Receptor Antagonist in the Management of Chronic Pancreatitis: A Phase 1 Trial

by Victor Ciofoaia, Wenqiang Chen, Bakain W. Tarek, Martha Gay, Narayan Shivapurkar and Jill P. Smith

Pharmaceutics 2024, 16(5), 611; https://doi.org/10.3390/pharmaceutics16050611 - 30 Apr 2024

Viewed by 992

Abstract

Chronic pancreatitis (CP) is a rare but debilitating condition with an 8-fold increased risk of developing pancreatic cancer. In addition to the symptoms that come from the loss of endocrine and exocrine function in CP, the management of chronic pain is problematic. We [...] Read more.

Chronic pancreatitis (CP) is a rare but debilitating condition with an 8-fold increased risk of developing pancreatic cancer. In addition to the symptoms that come from the loss of endocrine and exocrine function in CP, the management of chronic pain is problematic. We previously showed that the CCK-receptor antagonist called proglumide could decrease inflammation, acinar-ductal metaplasia, and fibrosis in murine models of CP. We hypothesized that proglumide would be safe and diminish pain caused by CP. A Phase 1 open-labeled safety study was performed in subjects with clinical and radiographic evidence of CP with moderate to severe pain. After a 4-week observation period, the subjects were treated with proglumide in 400 mg capsules three times daily (1200 mg per day) by mouth for 12 weeks, and then subjects returned for a safety visit 4 weeks after the discontinuation of the study medication. The results of three pain surveys (Numeric Rating Scale, COMPAT-SF, and NIH PROMIS) showed that the patients had significantly less pain after 12 weeks of proglumide compared to the pre-treatment observation phase. Of the eight subjects in this study, two experienced nausea and diarrhea with proglumide. These side effects resolved in one subject with doses reduced to 800 mg per day. No abnormalities were noted in the blood chemistries. A blood microRNA blood biomarker panel that corresponded to pancreatic inflammation and fibrosis showed significant improvement. We conclude that proglumide is safe and well tolerated in most subjects with CP at a dose of 1200 mg per day. Furthermore, proglumide therapy may have a beneficial effect by decreasing pain associated with CP. Full article

(This article belongs to the Special Issue New Pharmaceutical Targets to Counteract Chronic Inflammation)

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16 pages, 6430 KiB

Open AccessEditor’s ChoiceArticle

Linseed Oil-Based Oleogel Vehicles for Hydrophobic Drug Delivery—Physicochemical and Applicative Properties

by Sonia Kudłacik-Kramarczyk, Anna Drabczyk, Alicja Przybyłowicz and Marcel Krzan

Pharmaceutics 2024, 16(5), 600; https://doi.org/10.3390/pharmaceutics16050600 - 29 Apr 2024

Viewed by 671

Abstract

In this study, a methodology for synthesizing oleogels based on linseed oil and emulsifiers, such as beeswax and Tween 20 and Tween 80, was developed. Linseed oil served as the main oil phase, while beeswax acted as a gelling and emulsifying agent. Tween [...] Read more.

In this study, a methodology for synthesizing oleogels based on linseed oil and emulsifiers, such as beeswax and Tween 20 and Tween 80, was developed. Linseed oil served as the main oil phase, while beeswax acted as a gelling and emulsifying agent. Tween compounds are non-ionic surfactants composed of hydrophobic and hydrophilic parts, allowing for the formation of a stable system with promising properties. Surface wetting analysis of the obtained oleogels, FT-IR spectroscopy, and determination of relative and absolute humidity over time, as well as optical microscope analysis and rheological analysis of the obtained oleogels, were conducted as part of the research. The results indicate that increasing the amount of Tween 20 decreases the hydrophilicity of the oleogel, while Tween 80 exhibits the opposite effect. Surface energy analysis suggests that a higher content of Tween 20 may lead to a reduction in the surface energy of the oleogels, which may indicate greater material stability. Changes in relative humidity and FT-IR spectral analysis confirm the influence of emulsifiers on the presence of characteristic functional groups in the structure of the oleogels. Additionally, microscopic analysis suggests that an emulsifier with a longer hydrophobic tail leads to a denser material structure. Full article

(This article belongs to the Special Issue Functional Biomaterials in Biomedical Applications)

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24 pages, 3776 KiB

Open AccessEditor’s ChoiceArticle

Characterization of Surfactant Spheroidal Micelle Structure for Pharmaceutical Applications: A Novel Analytical Framework

by Liberato De Caro, Thibaud Stoll, Arnaud Grandeury, Fabia Gozzo and Cinzia Giannini

Pharmaceutics 2024, 16(5), 604; https://doi.org/10.3390/pharmaceutics16050604 - 29 Apr 2024

Viewed by 690

Abstract

We introduce an innovative theoretical framework tailored for the analysis of Pair Distribution Function (PDF) data derived from Small-Angle X-ray Scattering (SAXS) measurements of core-shell micelles. The new approach involves the exploitation of the first derivative of the PDF and the derivation of [...] Read more.

We introduce an innovative theoretical framework tailored for the analysis of Pair Distribution Function (PDF) data derived from Small-Angle X-ray Scattering (SAXS) measurements of core-shell micelles. The new approach involves the exploitation of the first derivative of the PDF and the derivation of analytical equations to solve the core-shell micelle structure under the hypothesis of a spheroidal shape. These analytical equations enable us to determine the micelle’s aggregation number, degree of ellipticity, and contrast in electron density between the core-shell and shell-buffer regions after having determined the whole micelle size and its shell size from the analysis of the first derivative of the PDF. We have formulated an overdetermined system of analytical equations based on the unknowns that characterize the micelle structure. This allows us to establish a Figure of Merit, which is utilized to identify the most reliable solution within the system of equations. Full article

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18 pages, 10346 KiB

Open AccessEditor’s ChoiceArticle

Development of 5-Fluorouracil/pH-Responsive Adjuvant-Embedded Extracellular Vesicles for Targeting α_vβ₃ Integrin Receptors in Tumors

by Jiseung Kim, Eunsol Lee and Eun Seong Lee

Pharmaceutics 2024, 16(5), 599; https://doi.org/10.3390/pharmaceutics16050599 - 29 Apr 2024

Viewed by 870

Abstract

To selectively target and treat murine melanoma B16BL6 tumors expressing α_vβ₃ integrin receptors, we engineered tumor-specific functional extracellular vesicles (EVs) tailored for the targeted delivery of antitumor drugs. This objective was achieved through the incorporation of a pH-responsive adjuvant, cyclic [...] Read more.

To selectively target and treat murine melanoma B16BL6 tumors expressing α_vβ₃ integrin receptors, we engineered tumor-specific functional extracellular vesicles (EVs) tailored for the targeted delivery of antitumor drugs. This objective was achieved through the incorporation of a pH-responsive adjuvant, cyclic arginine-glycine-aspartic acid peptide (cRGD, serving as a tumor-targeting ligand), and 5-fluorouracil (5-FU, employed as a model antitumor drug). The pH-responsive adjuvant, essential for modulating drug release, was synthesized by chemically conjugating 3-(diethylamino)propylamine (DEAP) to deoxycholic acid (DOCA, a lipophilic substance capable of integrating into EVs’ membranes), denoted as DEAP-DOCA. The DOCA, preactivated using N-(2-aminoethyl)maleimide (AEM), was chemically coupled with the thiol group of the cRGD-DOCA through the thiol–maleimide click reaction, resulting in the formation of cRGD-DOCA. Subsequently, DEAP-DOCA, cRGD-DOCA, and 5-FU were efficiently incorporated into EVs using a sonication method. The resulting tumor-targeting EVs, expressing cRGD ligands, demonstrated enhanced in vitro/in vivo cellular uptake specifically for B16BL6 tumors expressing α_vβ₃ integrin receptors. The ionization characteristics of the DEAP in DEAP-DOCA induced destabilization of the EVs membrane at pH 6.5 through protonation of the DEAP substance, thereby expediting 5-FU release. Consequently, an improvement in the in vivo antitumor efficacy was observed for B16BL6 tumors. Based on these comprehensive in vitro/in vivo findings, we anticipate that this EV system holds substantial promise as an exceptionally effective platform for antitumor therapeutic delivery. Full article

(This article belongs to the Special Issue Extracellular Vesicle-Based Drug Delivery Systems)

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15 pages, 2699 KiB

Open AccessEditor’s ChoiceArticle

Enhanced In Vitro Antiviral Activity of Ivermectin-Loaded Nanostructured Lipid Carriers against Porcine Epidemic Diarrhea Virus via Improved Intracellular Delivery

by Xiaolin Xu, Shasha Gao, Qindan Zuo, Jiahao Gong, Xinhao Song, Yongshi Liu, Jing Xiao, Xiaofeng Zhai, Haifeng Sun, Mingzhi Zhang, Xiuge Gao and Dawei Guo

Pharmaceutics 2024, 16(5), 601; https://doi.org/10.3390/pharmaceutics16050601 - 29 Apr 2024

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Abstract

Porcine epidemic diarrhea virus (PEDV) is an acute enteric coronavirus, inducing watery diarrhea and high mortality in piglets, leading to huge economic losses in global pig industry. Ivermectin (IVM), an FDA-approved antiparasitic agent, is characterized by high efficacy and wide applicability. However, the [...] Read more.

Porcine epidemic diarrhea virus (PEDV) is an acute enteric coronavirus, inducing watery diarrhea and high mortality in piglets, leading to huge economic losses in global pig industry. Ivermectin (IVM), an FDA-approved antiparasitic agent, is characterized by high efficacy and wide applicability. However, the poor bioavailability limits its application. Since the virus is parasitized inside the host cells, increasing the intracellular drug uptake can improve antiviral efficacy. Hence, we aimed to develop nanostructured lipid carriers (NLCs) to enhance the antiviral efficacy of IVM. The findings first revealed the capacity of IVM to inhibit the infectivity of PEDV by reducing viral replication with a certain direct inactivation effect. The as-prepared IVM-NLCs possessed hydrodynamic diameter of 153.5 nm with a zeta potential of −31.5 mV and high encapsulation efficiency (95.72%) and drug loading (11.17%). IVM interacted with lipids and was enveloped in lipid carriers with an amorphous state. Furthermore, its encapsulation in NLCs could enhance drug internalization. Meanwhile, IVM-NLCs inhibited PEDV proliferation by up to three orders of magnitude in terms of viral RNA copies, impeding the accumulation of reactive oxygen species and mitigating the mitochondrial dysfunction caused by PEDV infection. Moreover, IVM-NLCs markedly decreased the apoptosis rate of PEDV-induced Vero cells. Hence, IVM-NLCs showed superior inhibitory effect against PEDV compared to free IVM. Together, these results implied that NLCs is an efficient delivery system for IVM to improve its antiviral efficacy against PEDV via enhanced intracellular uptake. Full article

(This article belongs to the Special Issue Lipid/Polymer-Based Drug Delivery Systems)

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15 pages, 3790 KiB

Open AccessEditor’s ChoiceArticle

Targeted Thrombolysis with Magnetic Nanotherapeutics: A Translational Assessment

by Ming-Lu Lin, Siao-Yun Wu, Jyh-Ping Chen, Yi-Ching Lu, Shih-Ming Jung, Shiaw-Pyng Wey, Tony Wu and Yunn-Hwa Ma

Pharmaceutics 2024, 16(5), 596; https://doi.org/10.3390/pharmaceutics16050596 - 27 Apr 2024

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Abstract

Plasminogen activators, such as recombinant tissue-type plasminogen activators (rtPAs), while effective in treating thromboembolic diseases, often induce hemorrhagic complications due to non-specific enzyme activities in the systemic circulation. This study evaluated the targeting efficiency, efficacy, biodistribution, and potential toxicity of a rtPA covalently [...] Read more.

Plasminogen activators, such as recombinant tissue-type plasminogen activators (rtPAs), while effective in treating thromboembolic diseases, often induce hemorrhagic complications due to non-specific enzyme activities in the systemic circulation. This study evaluated the targeting efficiency, efficacy, biodistribution, and potential toxicity of a rtPA covalently attached to chitosan-coated magnetic nanoparticles (chitosan-MNP-rtPA). The thrombolytic activity of a chitosan-MNP-rtPA was preserved by protection from an endogenous plasminogen activator inhibitor-1 (PAI-1) in whole blood and after circulation in vivo, as examined by thromboelastometry. Single-photon emission computed tomography (SPECT) demonstrated real-time retention of a ^99mTc-MNP-rtPA induced by magnet application in a rat embolic model; an 80% reduction in rtPA dosage for a chitosan-MNP-rtPA with magnetic guidance was shown to restore blood flow. After treatment, iron deposition was observed in the reticuloendothelial systems, with portal edema and neutrophil infiltration in the liver at a ten-fold higher dose but not the regular dose. Nevertheless, no liver or renal toxicity was observed at this higher dose. In conclusion, the liver may still be the major deposit site of rtPA nanocomposites after targeted delivery; chitosan-coated MNPs are potentially amenable to target therapeutics with parenteral administration. Full article

(This article belongs to the Special Issue Recent Advances in Biomedical Applications of Magnetic Nanomaterials)

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19 pages, 5058 KiB

Open AccessEditor’s ChoiceArticle

Development and Efficacy Evaluation of Innovative Cosmetic Formulations with Caryocar brasiliense Fruit Pulp Oil Encapsulated in Freeze-Dried Liposomes

by Letícia Kakuda, Patrícia M. B. G. Maia Campos and Wanderley P. Oliveira

Pharmaceutics 2024, 16(5), 595; https://doi.org/10.3390/pharmaceutics16050595 - 27 Apr 2024

Viewed by 908

Abstract

Encapsulation and drying technologies allow the engineering of innovative raw materials from plant biodiversity, with potential applications in pharmaceutical and cosmetic fields. Lipid-based nanoencapsulation stands out for its efficiency, ease of production, and versatility in encapsulating substances, whether hydrophilic or lipophilic. This work [...] Read more.

Encapsulation and drying technologies allow the engineering of innovative raw materials from plant biodiversity, with potential applications in pharmaceutical and cosmetic fields. Lipid-based nanoencapsulation stands out for its efficiency, ease of production, and versatility in encapsulating substances, whether hydrophilic or lipophilic. This work aimed at encapsulating pequi oil in liposomes and freeze-dried liposomes to enhance its stability and functional benefits, such as skin hydration and anti-aging effects, for use in innovative cosmetic formulations. Pequi oil—extracted from the Caryocar brasiliense fruit pulp, a plant species from Brazilian plant biodiversity—is rich in secondary metabolites and fatty acids. Liposomes and dried liposomes offer controlled production processes and seamless integration into cosmetic formulations. The physicochemical analysis of the developed liposomes confirmed that the formulations are homogeneous and electrokinetically stable, as evidenced by consistent particle size distribution and zeta potential values, respectively. The gel-type formulations loaded with the dried liposomes exhibit enhanced skin hydration, improved barrier function, and refined microrelief, indicating improvements in skin conditions. These results highlight the potential of dried liposomes containing pequi oil for the development of innovative cosmeceutical products. This research contributes to the valorization of Brazilian biodiversity by presenting an innovative approach to leveraging the dermatological benefits of pequi oil in cosmetic applications. Full article

(This article belongs to the Special Issue Spray Drying and Encapsulation of Pharmaceuticals and Phytopharmaceuticals)

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