The 15th Anniversary of Pharmaceutics—Advances and Future Trends in Drug Delivery

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: closed (31 July 2024) | Viewed by 8718

Special Issue Editors


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Guest Editor
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy
Interests: molecularly imprinted polymers; drug delivery; drug targeting; theranostics; functional polymers; stimuli-responsive polymers; biomaterials
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy
Interests: molecularly imprinted polymers; drug delivery; drug targeting; theranostics; functional polymers; hydrogels; nanotechnology

Special Issue Information

Dear Colleagues,

The year 2023 marks the 15th anniversary of Pharmaceutics, and to celebrate this significant milestone, we aim to publish a Special Issue entitled “The 15th Anniversary of Pharmaceutics—Advances and Future Trends in Drug Delivery”.

Drug delivery can be defined as the process or method of administering a pharmaceutical compound to achieve a therapeutic effect both in humans or animals. The form in which a therapeutic agent is administered can exert an important impact on its efficacy and safety; thus, the use of suitable drug delivery systems (DDSs) can enhance both, leading to improved patient compliance.

In addition, the development of new drug molecules is expensive and time consuming, and DDSs represent new promising tools that can give a new life to old drugs by enabling controlled and/or targeted delivery, individualized therapy, real-time monitoring of therapeutic efficacy, improvements in stability, and the repositioning of exiting drugs for new therapeutic purposes.

In this Special Issue, original research articles and reviews are welcome.

We look forward to receiving your contributions.

Dr. Ortensia Ilaria Parisi
Dr. Marco Dattilo
Guest Editors

Manuscript Submission Information

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Keywords

  • drug delivery
  • drug targeting
  • theranostics
  • nanotechnology
  • in vitro and in vivo drug delivery model development
  • drug repurposing
  • stimuli-responsive systems

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Published Papers (6 papers)

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Research

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23 pages, 3248 KiB  
Article
Lipid-Based Gels for Delivery of 3-O-Ethyl L-Ascorbic acid in Topical Applications
by Noèlia Loza-Rodríguez, Aina Millán-Sánchez, Mireia Mallandrich, Ana Cristina Calpena and Olga López
Pharmaceutics 2024, 16(9), 1187; https://doi.org/10.3390/pharmaceutics16091187 - 7 Sep 2024
Viewed by 1107
Abstract
This study explores the incorporation of 10% 3-O-ethyl L-ascorbic acid (ETVC), a derivative of vitamin C, into two lipid gel systems: a hydrogel (HG) consisting exclusively of lipids and water and a bigel (BG) combining the hydrogel with an oleogel made from olive [...] Read more.
This study explores the incorporation of 10% 3-O-ethyl L-ascorbic acid (ETVC), a derivative of vitamin C, into two lipid gel systems: a hydrogel (HG) consisting exclusively of lipids and water and a bigel (BG) combining the hydrogel with an oleogel made from olive oil and beeswax. We investigated the ETVC release profiles from both materials using synthetic membranes and measured their permeation through porcine skin in vitro. Additionally, the interaction of these lipid gel systems with the stratum corneum (SC) was determined. Results from the release study indicate that the BG exhibited slower ETVC release compared to the HG. The permeation experiments showed that the presence of lipids in the formulations enhanced ETVC retention in the skin. The HG delivered a higher amount to the SC, while the BG achieved greater retention in the epidermis. This difference is attributed to the different lipophilic nature of each material. The structural analysis of SC lipids revealed that the organization of surface lipids remained unaltered by the application of the gels. Finally, an in vitro efficacy test in porcine skin using methylene blue indicated that our ETVC gels exhibited antioxidant activity. These findings provide valuable insights into the potential of lipid-based gels for topical applications. Full article
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22 pages, 2852 KiB  
Article
Upgrading Mitochondria-Targeting Peptide-Based Nanocomplexes for Zebrafish In Vivo Compatibility Assays
by Rúben Faria, Eric Vivès, Prisca Boisguérin, Simon Descamps, Ângela Sousa and Diana Costa
Pharmaceutics 2024, 16(7), 961; https://doi.org/10.3390/pharmaceutics16070961 - 20 Jul 2024
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Abstract
The lack of effective delivery systems has slowed the development of mitochondrial gene therapy. Delivery systems based on cell-penetrating peptides (CPPs) like the WRAP (tryptophan and arginine-rich peptide) family conjugated with a mitochondrial targeting sequence (MTS) have emerged as adequate carriers to mediate [...] Read more.
The lack of effective delivery systems has slowed the development of mitochondrial gene therapy. Delivery systems based on cell-penetrating peptides (CPPs) like the WRAP (tryptophan and arginine-rich peptide) family conjugated with a mitochondrial targeting sequence (MTS) have emerged as adequate carriers to mediate gene expression into the mitochondria. In this work, we performed the PEGylation of WRAP/pDNA nanocomplexes and compared them with previously analyzed nanocomplexes such as (KH)9/pDNA and CpMTP/pDNA. All nanocomplexes exhibited nearly homogeneous sizes between 100 and 350 nm in different environments. The developed complexes were biocompatible and hemocompatible to both human astrocytes and lung smooth muscle cells, ensuring in vivo safety. The nanocomplexes displayed mitochondria targeting ability, as through transfection they preferentially accumulate into the mitochondria of astrocytes and muscle cells to the detriment of cytosol and lysosomes. Moreover, the transfection of these cells with MTS–CPP/pDNA complexes produced significant levels of mitochondrial protein ND1, highlighting their efficient role as gene delivery carriers toward mitochondria. The positive obtained data pave the way for in vivo research. Using confocal microscopy, the cellular internalization capacity of these nanocomplexes in the zebrafish embryo model was assessed. The peptide-based nanocomplexes were easily internalized into zebrafish embryos, do not cause harmful or toxic effects, and do not affect zebrafish’s normal development and growth. These promising results indicate that MTS–CPP complexes are stable nanosystems capable of internalizing in vivo models and do not present associated toxicity. This work, even at an early stage, offers good prospects for continued in vivo zebrafish research to evaluate the performance of nanocomplexes for mitochondrial gene therapy. Full article
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14 pages, 4117 KiB  
Article
Engineered Hybrid Vesicles and Cellular Internalization in Mammary Cancer Cells
by So Yun Kim, Dagyeong Guk, Youngdo Jeong, Eunji Kim, Hansol Kim and Sung Tae Kim
Pharmaceutics 2024, 16(4), 440; https://doi.org/10.3390/pharmaceutics16040440 - 22 Mar 2024
Cited by 1 | Viewed by 1779
Abstract
Extracellular vesicles play an important role in intercellular communication, with the potential to serve as biomaterials for nanocarriers. Combining such extracellular vesicles and liposomes results in advanced drug delivery carriers. In this study, we attempted to fabricate hybrid vesicles using a membrane fusion [...] Read more.
Extracellular vesicles play an important role in intercellular communication, with the potential to serve as biomaterials for nanocarriers. Combining such extracellular vesicles and liposomes results in advanced drug delivery carriers. In this study, we attempted to fabricate hybrid vesicles using a membrane fusion method and incorporated an anticancer drug. As a result, we successfully prepared nanosized uniform hybrid vesicles and evaluated their physicochemical characteristics and intracellular uptake mechanisms via endocytosis in various cell lines. Compared to liposomes, the hybrid vesicles showed better physical properties and a relatively higher reduction in cell viability, which was presumably dependent on the specific cell type. These findings suggest that fusion-based hybrid vesicles offer a novel strategy for delivering therapeutic agents and provide insights into the types of extracellular vesicles that are useful in fabricating hybrid vesicles to develop an advanced drug delivery system. Full article
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11 pages, 4535 KiB  
Article
Human β-Defensin 23 as a Carrier for In Vitro and In Vivo Delivery of mRNA
by Kyoung-Ran Kim, Junghyun Kim, Seunghye Cho and Dae-Ro Ahn
Pharmaceutics 2023, 15(10), 2477; https://doi.org/10.3390/pharmaceutics15102477 - 17 Oct 2023
Viewed by 1132
Abstract
The successful application of mRNA therapeutics hinges on the effective intracellular delivery of mRNA both in vitro and in vivo. However, this remains a formidable challenge due to the polyanionic nature, longitudinal shape, and low nuclease resistance of mRNA. In this study, we [...] Read more.
The successful application of mRNA therapeutics hinges on the effective intracellular delivery of mRNA both in vitro and in vivo. However, this remains a formidable challenge due to the polyanionic nature, longitudinal shape, and low nuclease resistance of mRNA. In this study, we introduce a novel mRNA delivery platform utilizing a human β-defensin peptide, hBD23. The positive charge of hBD23 allows it to form nanocomplexes with mRNA, facilitating cellular uptake and providing protection against serum nucleases. When optimized for peptide-to-mRNA (N/P) ratios, these hBD23/mRNA complexes demonstrated efficient cellular delivery and subsequent protein expression both in vitro and in vivo. Importantly, as hBD23 is human derived, the complexes exhibited minimal cytotoxicity and immunogenicity. Given its high biocompatibility and delivery efficiency, hBD23 represents a promising platform for the in vitro and in vivo delivery of mRNA. Full article
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Review

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28 pages, 2664 KiB  
Review
Exploring Protein-Based Carriers in Drug Delivery: A Review
by Claudia Ferraro, Marco Dattilo, Francesco Patitucci, Sabrina Prete, Giuseppe Scopelliti, Ortensia Ilaria Parisi and Francesco Puoci
Pharmaceutics 2024, 16(9), 1172; https://doi.org/10.3390/pharmaceutics16091172 - 5 Sep 2024
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Abstract
Drug delivery systems (DDSs) represent an emerging focus for many researchers and they are becoming progressively crucial in the development of new treatments. Great attention is given to all the challenges that a drug has to overcome during its journey across barriers and [...] Read more.
Drug delivery systems (DDSs) represent an emerging focus for many researchers and they are becoming progressively crucial in the development of new treatments. Great attention is given to all the challenges that a drug has to overcome during its journey across barriers and tissues and all the pharmacokinetics modulations that are needed in order to reach the targeting sites. The goal of these pathways is the delivery of drugs in a controlled way, optimizing their bioavailability and minimizing side effects. Recent innovations in DDSs include various nanotechnology-based approaches, such as nanoparticles, nanofibers and micelles, which provide effective targeted delivery and sustained release of therapeutics. In this context, protein-based drug delivery systems are gaining significant attention in the pharmaceutical field due to their potential to revolutionize targeted and efficient drug delivery. As natural biomolecules, proteins offer distinct advantages, including safety, biocompatibility and biodegradability, making them a fascinating alternative to synthetic polymers. Moreover, protein-based carriers, including those derived from gelatin, albumin, collagen, gliadin and silk proteins, demonstrate exceptional stability under physiological conditions, and they allow for controlled and sustained drug release, enhancing therapeutic efficacy. This review provides a comprehensive overview of the current trends, challenges, and future perspectives in protein-based drug delivery, focusing on the types of proteins adopted and the techniques that are being developed to enhance their functionality in terms of drug affinity and targeting capabilities, underscoring their potential to significantly impact modern therapeutics. Full article
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23 pages, 1109 KiB  
Review
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 1835
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
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