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Open AccessEditorial

Feature Reviews in Pharmaceutical Technology

by Silviya Petrova Zustiak and Era Jain

Pharmaceuticals 2023, 16(10), 1336; https://doi.org/10.3390/ph16101336 - 22 Sep 2023

Viewed by 1109

Abstract

We are excited to present the Special Issue, “Feature Reviews in Pharmaceutical Technology”, aiming to highlight exciting developments in pharmaceutical technologies [...] Full article

(This article belongs to the Special Issue Feature Reviews in Pharmaceutical Technology)

Review

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30 pages, 1071 KiB

Open AccessReview

Drug Delivery Strategies and Nanozyme Technologies to Overcome Limitations for Targeting Oxidative Stress in Osteoarthritis

by Jessica Lee Aldrich, Arjun Panicker, Robert Ovalle, Jr. and Blanka Sharma

Pharmaceuticals 2023, 16(7), 1044; https://doi.org/10.3390/ph16071044 - 23 Jul 2023

Cited by 7 | Viewed by 3421

Abstract

Oxidative stress is an important, but elusive, therapeutic target for osteoarthritis (OA). Antioxidant strategies that target oxidative stress through the elimination of reactive oxygen species (ROS) have been widely evaluated for OA but are limited by the physiological characteristics of the joint. Current [...] Read more.

Oxidative stress is an important, but elusive, therapeutic target for osteoarthritis (OA). Antioxidant strategies that target oxidative stress through the elimination of reactive oxygen species (ROS) have been widely evaluated for OA but are limited by the physiological characteristics of the joint. Current hallmarks in antioxidant treatment strategies include poor bioavailability, poor stability, and poor retention in the joint. For example, oral intake of exogenous antioxidants has limited access to the joint space, and intra-articular injections require frequent dosing to provide therapeutic effects. Advancements in ROS-scavenging nanomaterials, also known as nanozymes, leverage bioactive material properties to improve delivery and retention. Material properties of nanozymes can be tuned to overcome physiological barriers in the knee. However, the clinical application of these nanozymes is still limited, and studies to understand their utility in treating OA are still in their infancy. The objective of this review is to evaluate current antioxidant treatment strategies and the development of nanozymes as a potential alternative to conventional small molecules and enzymes. Full article

(This article belongs to the Special Issue Feature Reviews in Pharmaceutical Technology)

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19 pages, 1713 KiB

Open AccessReview

Laponite-Based Nanocomposite Hydrogels for Drug Delivery Applications

by Samuel T. Stealey, Akhilesh K. Gaharwar and Silviya Petrova Zustiak

Pharmaceuticals 2023, 16(6), 821; https://doi.org/10.3390/ph16060821 - 31 May 2023

Cited by 25 | Viewed by 5436

Abstract

Hydrogels are widely used for therapeutic delivery applications due to their biocompatibility, biodegradability, and ability to control release kinetics by tuning swelling and mechanical properties. However, their clinical utility is hampered by unfavorable pharmacokinetic properties, including high initial burst release and difficulty in [...] Read more.

Hydrogels are widely used for therapeutic delivery applications due to their biocompatibility, biodegradability, and ability to control release kinetics by tuning swelling and mechanical properties. However, their clinical utility is hampered by unfavorable pharmacokinetic properties, including high initial burst release and difficulty in achieving prolonged release, especially for small molecules (<500 Da). The incorporation of nanomaterials within hydrogels has emerged as viable option as a method to trap therapeutics within the hydrogel and sustain release kinetics. Specifically, two-dimensional nanosilicate particles offer a plethora of beneficial characteristics, including dually charged surfaces, degradability, and enhanced mechanical properties within hydrogels. The nanosilicate–hydrogel composite system offers benefits not obtainable by just one component, highlighting the need for detail characterization of these nanocomposite hydrogels. This review focuses on Laponite, a disc-shaped nanosilicate with diameter of 30 nm and thickness of 1 nm. The benefits of using Laponite within hydrogels are explored, as well as examples of Laponite–hydrogel composites currently being investigated for their ability to prolong the release of small molecules and macromolecules such as proteins. Future work will further characterize the interplay between nanosilicates, hydrogel polymer, and encapsulated therapeutics, and how each of these components affect release kinetics and mechanical properties. Full article

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32 pages, 2384 KiB

Open AccessEditor’s ChoiceReview

Recent Advances in Doxorubicin Formulation to Enhance Pharmacokinetics and Tumor Targeting

by Jihoon Lee, Min-Koo Choi and Im-Sook Song

Pharmaceuticals 2023, 16(6), 802; https://doi.org/10.3390/ph16060802 - 29 May 2023

Cited by 39 | Viewed by 10643

Abstract

Doxorubicin (DOX), a widely used drug in cancer chemotherapy, induces cell death via multiple intracellular interactions, generating reactive oxygen species and DNA-adducted configurations that induce apoptosis, topoisomerase II inhibition, and histone eviction. Despite its wide therapeutic efficacy in solid tumors, DOX often induces [...] Read more.

Doxorubicin (DOX), a widely used drug in cancer chemotherapy, induces cell death via multiple intracellular interactions, generating reactive oxygen species and DNA-adducted configurations that induce apoptosis, topoisomerase II inhibition, and histone eviction. Despite its wide therapeutic efficacy in solid tumors, DOX often induces drug resistance and cardiotoxicity. It shows limited intestinal absorption because of low paracellular permeability and P-glycoprotein (P-gp)-mediated efflux. We reviewed various parenteral DOX formulations, such as liposomes, polymeric micelles, polymeric nanoparticles, and polymer-drug conjugates, under clinical use or trials to increase its therapeutic efficacy. To improve the bioavailability of DOX in intravenous and oral cancer treatment, studies have proposed a pH- or redox-sensitive and receptor-targeted system for overcoming DOX resistance and increasing therapeutic efficacy without causing DOX-induced toxicity. Multifunctional formulations of DOX with mucoadhesiveness and increased intestinal permeability through tight-junction modulation and P-gp inhibition have also been used as orally bioavailable DOX in the preclinical stage. The increasing trends of developing oral formulations from intravenous formulations, the application of mucoadhesive technology, permeation-enhancing technology, and pharmacokinetic modulation with functional excipients might facilitate the further development of oral DOX. Full article

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26 pages, 3611 KiB

Open AccessReview

The Therapeutic Potential of Novel Carnosine Formulations: Perspectives for Drug Development

by Angela Bonaccorso, Anna Privitera, Margherita Grasso, Sonya Salamone, Claudia Carbone, Rosario Pignatello, Teresa Musumeci, Filippo Caraci and Giuseppe Caruso

Pharmaceuticals 2023, 16(6), 778; https://doi.org/10.3390/ph16060778 - 23 May 2023

Cited by 8 | Viewed by 4209

Abstract

Carnosine (beta-alanyl-L-histidine) is an endogenous dipeptide synthesized via the activity of the ATP-dependent enzyme carnosine synthetase 1 and can be found at a very high concentration in tissues with a high metabolic rate, including muscles (up to 20 mM) and brain (up to [...] Read more.

Carnosine (beta-alanyl-L-histidine) is an endogenous dipeptide synthesized via the activity of the ATP-dependent enzyme carnosine synthetase 1 and can be found at a very high concentration in tissues with a high metabolic rate, including muscles (up to 20 mM) and brain (up to 5 mM). Because of its well-demonstrated multimodal pharmacodynamic profile, which includes anti-aggregant, antioxidant, and anti-inflammatory activities, as well as its ability to modulate the energy metabolism status in immune cells, this dipeptide has been investigated in numerous experimental models of diseases, including Alzheimer’s disease, and at a clinical level. The main limit for the therapeutic use of carnosine is related to its rapid hydrolysis exerted by carnosinases, especially at the plasma level, reason why the development of new strategies, including the chemical modification of carnosine or its vehiculation into innovative drug delivery systems (DDS), aiming at increasing its bioavailability and/or at facilitating the site-specific transport to different tissues, is of utmost importance. In the present review, after a description of carnosine structure, biological activities, administration routes, and metabolism, we focused on different DDS, including vesicular systems and metallic nanoparticles, as well as on possible chemical derivatization strategies related to carnosine. In particular, a basic description of the DDS employed or the derivatization/conjugation applied to obtain carnosine formulations, followed by the possible mechanism of action, is given. To the best of our knowledge, this is the first review that includes all the new formulations of carnosine (DDS and derivatives), allowing a decrease or complete prevention of the hydrolysis of this dipeptide exerted by carnosinases, the simultaneous blood–brain barrier crossing, the maintenance or enhancement of carnosine biological activity, and the site-specific transport to different tissues, which then offers perspectives for the development of new drugs. Full article

(This article belongs to the Special Issue Feature Reviews in Pharmaceutical Technology)

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18 pages, 1960 KiB

Open AccessReview

Patient-Centric Design of Topical Dermatological Medicines

by Rita Oliveira and Isabel F. Almeida

Pharmaceuticals 2023, 16(4), 617; https://doi.org/10.3390/ph16040617 - 19 Apr 2023

Cited by 9 | Viewed by 3763

Abstract

Topical treatments are essential approaches to skin diseases but are associated with poor adherence. Topical vehicles have the primary purpose of ensuring drug effectiveness (by modulating drug stability and delivery, as well as skin properties) but have a marked impact on treatment outcomes [...] Read more.

Topical treatments are essential approaches to skin diseases but are associated with poor adherence. Topical vehicles have the primary purpose of ensuring drug effectiveness (by modulating drug stability and delivery, as well as skin properties) but have a marked impact on treatment outcomes as they influence patient satisfaction and, consequently, adherence to topical treatments. There is also a wide variety of vehicles available for topical formulations, which can complicate the decisions of clinicians regarding the most appropriate treatments for specific skin disorders. One of the possible strategies to improve topical-treatment adherence is the implementation of patient-centric drug-product design. In this process, the patient’s needs (e.g., those related to motor impairment), the needs associated with the disease (according to the skin lesions’ characteristics), and the patient’s preferences are taken into consideration and translated into a target product profile (TPP). Herein, an overview of topical vehicles and their properties is presented, along with a discussion of the patient-centric design of topical dermatological medicines and the proposal of TPPs for some of the most common skin diseases. Full article

(This article belongs to the Special Issue Feature Reviews in Pharmaceutical Technology)

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42 pages, 7466 KiB

Open AccessReview

Exploring the Application of Micellar Drug Delivery Systems in Cancer Nanomedicine

by Qi Wang, Keerthi Atluri, Amit K. Tiwari and R. Jayachandra Babu

Pharmaceuticals 2023, 16(3), 433; https://doi.org/10.3390/ph16030433 - 12 Mar 2023

Cited by 36 | Viewed by 14924

Abstract

Various formulations of polymeric micelles, tiny spherical structures made of polymeric materials, are currently being investigated in preclinical and clinical settings for their potential as nanomedicines. They target specific tissues and prolong circulation in the body, making them promising cancer treatment options. This [...] Read more.

Various formulations of polymeric micelles, tiny spherical structures made of polymeric materials, are currently being investigated in preclinical and clinical settings for their potential as nanomedicines. They target specific tissues and prolong circulation in the body, making them promising cancer treatment options. This review focuses on the different types of polymeric materials available to synthesize micelles, as well as the different ways that micelles can be tailored to be responsive to different stimuli. The selection of stimuli-sensitive polymers used in micelle preparation is based on the specific conditions found in the tumor microenvironment. Additionally, clinical trends in using micelles to treat cancer are presented, including what happens to micelles after they are administered. Finally, various cancer drug delivery applications involving micelles are discussed along with their regulatory aspects and future outlooks. As part of this discussion, we will examine current research and development in this field. The challenges and barriers they may have to overcome before they can be widely adopted in clinics will also be discussed. Full article

(This article belongs to the Special Issue Feature Reviews in Pharmaceutical Technology)

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27 pages, 2872 KiB

Open AccessReview

Application of Design of Experiments in the Development of Self-Microemulsifying Drug Delivery Systems

by Chien-Ming Hsieh, Ting-Lun Yang, Athika Darumas Putri and Chin-Tin Chen

Pharmaceuticals 2023, 16(2), 283; https://doi.org/10.3390/ph16020283 - 13 Feb 2023

Cited by 17 | Viewed by 4765

Abstract

Oral delivery has become the route of choice among all other types of drug administrations. However, typical chronic disease drugs are often poorly water-soluble, have low dissolution rates, and undergo first-pass metabolism, ultimately leading to low bioavailability and lack of efficacy. The lipid-based [...] Read more.

Oral delivery has become the route of choice among all other types of drug administrations. However, typical chronic disease drugs are often poorly water-soluble, have low dissolution rates, and undergo first-pass metabolism, ultimately leading to low bioavailability and lack of efficacy. The lipid-based formulation offers tremendous benefits of using versatile excipients and has great compatibility with all types of dosage forms. Self-microemulsifying drug delivery system (SMEDDS) promotes drug self-emulsification in a combination of oil, surfactant, and co-surfactant, thereby facilitating better drug solubility and absorption. The feasible preparation of SMEDDS creates a promising strategy to improve the drawbacks of lipophilic drugs administered orally. Selecting a decent mixing among these components is, therefore, of importance for successful SMEDDS. Quality by Design (QbD) brings a systematic approach to drug development, and it offers promise to significantly improve the manufacturing quality performance of SMEDDS. Furthermore, it could be benefited efficiently by conducting pre-formulation studies integrated with the statistical design of experiment (DoE). In this review, we highlight the recent findings for the development of microemulsions and SMEDDS by using DoE methods to optimize the formulations for drugs in different excipients with controllable ratios. A brief overview of DoE concepts is discussed, along with its technical benefits in improving SMEDDS formulations. Full article

(This article belongs to the Special Issue Feature Reviews in Pharmaceutical Technology)

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17 pages, 1276 KiB

Open AccessReview

KIF1A-Associated Neurological Disorder: An Overview of a Rare Mutational Disease

by Ayushi Nair, Alosh Greeny, Rajalakshmi Rajendran, Mohamed A. Abdelgawad, Mohammed M. Ghoneim, Roshni Pushpa Raghavan, Sachithra Thazhathuveedu Sudevan, Bijo Mathew and Hoon Kim

Pharmaceuticals 2023, 16(2), 147; https://doi.org/10.3390/ph16020147 - 19 Jan 2023

Cited by 10 | Viewed by 6327

Abstract

KIF1A-associated neurological diseases (KANDs) are a group of inherited conditions caused by changes in the microtubule (MT) motor protein KIF1A as a result of KIF1A gene mutations. Anterograde transport of membrane organelles is facilitated by the kinesin family protein encoded by the MT-based [...] Read more.

KIF1A-associated neurological diseases (KANDs) are a group of inherited conditions caused by changes in the microtubule (MT) motor protein KIF1A as a result of KIF1A gene mutations. Anterograde transport of membrane organelles is facilitated by the kinesin family protein encoded by the MT-based motor gene KIF1A. Variations in the KIF1A gene, which primarily affect the motor domain, disrupt its ability to transport synaptic vesicles containing synaptophysin and synaptotagmin leading to various neurological pathologies such as hereditary sensory neuropathy, autosomal dominant and recessive forms of spastic paraplegia, and different neurological conditions. These mutations are frequently misdiagnosed because they result from spontaneous, non-inherited genomic alterations. Whole-exome sequencing (WES), a cutting-edge method, assists neurologists in diagnosing the illness and in planning and choosing the best course of action. These conditions are simple to be identified in pediatric and have a life expectancy of 5–7 years. There is presently no permanent treatment for these illnesses, and researchers have not yet discovered a medicine to treat them. Scientists have more hope in gene therapy since it can be used to cure diseases brought on by mutations. In this review article, we discussed some of the experimental gene therapy methods, including gene replacement, gene knockdown, symptomatic gene therapy, and cell suicide gene therapy. It also covered its clinical symptoms, pathogenesis, current diagnostics, therapy, and research advances currently occurring in the field of KAND-related disorders. This review also explained the impact that gene therapy can be designed in this direction and afford the remarkable benefits to the patients and society. Full article

(This article belongs to the Special Issue Feature Reviews in Pharmaceutical Technology)

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35 pages, 2405 KiB

Open AccessReview

Gastrointestinal Permeation Enhancers for the Development of Oral Peptide Pharmaceuticals

by Jae Cheon Kim, Eun Ji Park and Dong Hee Na

Pharmaceuticals 2022, 15(12), 1585; https://doi.org/10.3390/ph15121585 - 19 Dec 2022

Cited by 19 | Viewed by 10388

Abstract

Recently, two oral-administered peptide pharmaceuticals, semaglutide and octreotide, have been developed and are considered as a breakthrough in peptide and protein drug delivery system development. In 2019, the Food and Drug Administration (FDA) approved an oral dosage form of semaglutide developed by Novo [...] Read more.

Recently, two oral-administered peptide pharmaceuticals, semaglutide and octreotide, have been developed and are considered as a breakthrough in peptide and protein drug delivery system development. In 2019, the Food and Drug Administration (FDA) approved an oral dosage form of semaglutide developed by Novo Nordisk (Rybelsus^®) for the treatment of type 2 diabetes. Subsequently, the octreotide capsule (Mycapssa^®), developed through Chiasma’s Transient Permeation Enhancer (TPE) technology, also received FDA approval in 2020 for the treatment of acromegaly. These two oral peptide products have been a significant success; however, a major obstacle to their oral delivery remains the poor permeability of peptides through the intestinal epithelium. Therefore, gastrointestinal permeation enhancers are of great relevance for the development of subsequent oral peptide products. Sodium salcaprozate (SNAC) and sodium caprylate (C8) have been used as gastrointestinal permeation enhancers for semaglutide and octreotide, respectively. Herein, we briefly review two approved products, Rybelsus^® and Mycapssa^®, and discuss the permeation properties of SNAC and medium chain fatty acids, sodium caprate (C10) and C8, focusing on Eligen technology using SNAC, TPE technology using C8, and gastrointestinal permeation enhancement technology (GIPET) using C10. Full article

(This article belongs to the Special Issue Feature Reviews in Pharmaceutical Technology)

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14 pages, 620 KiB

Open AccessReview

Renal Proximal Tubular Cells: A New Site for Targeted Delivery Therapy of Diabetic Kidney Disease

by Hao Li, Wenni Dai, Zhiwen Liu and Liyu He

Pharmaceuticals 2022, 15(12), 1494; https://doi.org/10.3390/ph15121494 - 30 Nov 2022

Cited by 8 | Viewed by 3529

Abstract

Diabetic kidney disease (DKD) is a major complication of diabetes mellitus (DM) and the leading cause of end-stage kidney disease (ESKD) worldwide. A significant number of drugs have been clinically investigated for the treatment of DKD. However, a large proportion of patients still [...] Read more.

Diabetic kidney disease (DKD) is a major complication of diabetes mellitus (DM) and the leading cause of end-stage kidney disease (ESKD) worldwide. A significant number of drugs have been clinically investigated for the treatment of DKD. However, a large proportion of patients still develop end-stage kidney disease unstoppably. As a result, new effective therapies are urgently needed to slow down the progression of DKD. Recently, there is increasing evidence that targeted drug delivery strategies such as large molecule carriers, small molecule prodrugs, and nanoparticles can improve drug efficacy and reduce adverse side effects. There is no doubt that targeted drug delivery strategies have epoch-making significance and great application prospects for the treatment of DKD. In addition, the proximal tubule plays a very critical role in the progression of DKD. Consequently, the purpose of this paper is to summarize the current understanding of proximal tubule cell-targeted therapy, screen for optimal targeting strategies, and find new therapeutic approaches for the treatment of DKD. Full article

(This article belongs to the Special Issue Feature Reviews in Pharmaceutical Technology)

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19 pages, 1062 KiB

Open AccessReview

Commercially Available Enteric Empty Hard Capsules, Production Technology and Application

by Aleš Franc, David Vetchý and Nicole Fülöpová

Pharmaceuticals 2022, 15(11), 1398; https://doi.org/10.3390/ph15111398 - 13 Nov 2022

Cited by 14 | Viewed by 11962

Abstract

Currently, there is a growing need to prepare small batches of enteric capsules for individual therapy or clinical evaluation since many acidic-sensitive substances should be protected from the stomach’s acidic environment, including probiotics or fecal material, in the fecal microbiota transplantation (FMT) process. [...] Read more.

Currently, there is a growing need to prepare small batches of enteric capsules for individual therapy or clinical evaluation since many acidic-sensitive substances should be protected from the stomach’s acidic environment, including probiotics or fecal material, in the fecal microbiota transplantation (FMT) process. A suitable method seems to be the encapsulation of drugs or lyophilized alternatively frozen biological suspensions in commercial hard enteric capsules prepared by so-called Enteric Capsule Drug Delivery Technology (ECDDT). Manufacturers supply these types of capsules, made from pH-soluble polymers, in products such as AR Caps^®, EnTRinsic^TM, and Vcaps^® Enteric, or capsules made of gelling polymers that release their content as the gel erodes over time when passing through the digestive tract. These include DRcaps^®, EMBO CAPS^® AP, BioVXR^®, or ACGcaps™ HD. Although not all capsules in all formulations meet pharmaceutical requirements for delayed-release dosage forms in disintegration and dissolution tests, they usually find practical application. This literature review presents their composition and properties. Since ECDDT is a new technology, this article is based on a limited number of references. Full article

(This article belongs to the Special Issue Feature Reviews in Pharmaceutical Technology)

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19 pages, 2070 KiB

Open AccessReview

Digital Pills with Ingestible Sensors: Patent Landscape Analysis

by Olena Litvinova, Elisabeth Klager, Nikolay T. Tzvetkov, Oliver Kimberger, Maria Kletecka-Pulker, Harald Willschke and Atanas G. Atanasov

Pharmaceuticals 2022, 15(8), 1025; https://doi.org/10.3390/ph15081025 - 19 Aug 2022

Cited by 24 | Viewed by 8403

Abstract

The modern healthcare system is directly related to the development of digital health tools and solutions. Pills with digital sensors represent a highly innovative class of new pharmaceuticals. The aim of this work was to analyze the patent landscape and to systematize the [...] Read more.

The modern healthcare system is directly related to the development of digital health tools and solutions. Pills with digital sensors represent a highly innovative class of new pharmaceuticals. The aim of this work was to analyze the patent landscape and to systematize the main trends in patent protection of digital pills with ingestible sensors worldwide; accordingly, to identify the patenting leaders as well as the main prevailing areas of therapy for patent protection, and the future perspectives in the field. In July 2022, a search was conducted using Internet databases, such as the EPO, USPTO, FDA and the Lens database. The patent landscape analysis shows an increase in the number of patents related to digital pills with ingestible sensors for mobile clinical monitoring, smart drug delivery, and endoscopy diagnostics. The leaders in the number of patents issued are the United States, the European Patent Office, Canada, Australia, and China. The following main areas of patenting digital pills with ingestible sensors were identified: treatment in the field of mental health; HIV/AIDS; pain control; cardiovascular diseases; diabetes; gastroenterology (including hepatitis C); oncology; tuberculosis; and transplantology. The development of scientific and practical approaches towards the implementation of effective and safe digital pills will improve treatment outcomes, increase compliance, reduce hospital stays, provide mobile clinical monitoring, have a positive impact on treatment costs and will contribute to increased patient safety. Full article

(This article belongs to the Special Issue Feature Reviews in Pharmaceutical Technology)

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