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Pharmaceutics
Special Issues
Advances in Delivery of Peptides and Proteins
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Advances in Delivery of Peptides and Proteins

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

Deadline for manuscript submissions: 30 September 2025 | Viewed by 2044

Special Issue Editors

Prof. Dr. Jingyuan Wen

E-Mail Website
Guest Editor
School of Pharmacy, Faculty of Medical and Health Sciences, The University of Auckland, Auckland 1010, New Zealand
Interests: transdermal drug delivery; topical drug delivery; lipid-based delivery systems; nanocarriers; antioxidants; sustained or controlled-release formulations; oral delivery of proteins and peptides; tumor targeting
Special Issues, Collections and Topics in MDPI journals
Dr. Mengyang Liu

E-Mail Website
Guest Editor
School of Pharmacy, Faculty of Medical and Health Sciences, The University of Auckland, Auckland 1010, New Zealand
Interests: transdermal and dermal delivery; nanoparticulate delivery system; skin barriers; peptide drug delivery

Special Issue Information

Dear Colleagues,

The following Special Issue, entitled "Advances in Delivery of Peptides and Proteins," focuses on the critical role peptides and proteins play as therapeutic agents in treating various diseases. Despite their therapeutic potential, the effective delivery of these macromolecules presents significant challenges due to their large molecular size, instability, and vulnerability to degradation. Thus, developing innovative delivery systems is vital to improve their bioavailability, stability, and precise targeting.

Recent advancements in areas such as nanotechnology, encapsulation techniques, and novel formulation strategies have provided promising solutions for overcoming these challenges. This Special Issue aims to highlight the latest research and technological innovations in peptide and protein delivery, particularly emphasising novel approaches and methodologies that address existing delivery limitations.

Contributions are welcome on topics such as nanoparticle-based delivery, controlled release systems, and advanced strategies to enhance oral, transdermal, and injectable delivery routes. By bringing together cutting-edge research, this Special Issue offers a comprehensive overview of current trends and future directions in peptide and protein delivery.

We look forward to receiving your contributions.

Prof. Dr. Jingyuan Wen
Dr. Mengyang Liu
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • peptide delivery
  • protein delivery
  • bioavailability
  • stability
  • nanoparticles
  • encapsulation
  • controlled release
  • pharmaceutical innovation

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Published Papers (3 papers)

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Research

15 pages, 1485 KiB  
Article
Novel Delivery of Cyclic-Diguanylate Monophosphate Utilizing Amyloid Depots
by Maytham Ismail, Benjamin Beluzo, Sergei Chuikov, Venkateshwar G. Keshamouni and Mathumai Kanapathipillai
Pharmaceutics 2025, 17(5), 668; https://doi.org/10.3390/pharmaceutics17050668 - 19 May 2025
Viewed by 228
Abstract
Background: Recently, cyclic diguanylate monophosphate (c-di-GMP) drug delivery has garnered interest due to its potential in cancer immune modulation. In this pilot study, we developed a novel c-di-GMP formulation based on peptide amyloids. The amyloid depots were formed by combining an amyloidogenic prone [...] Read more.
Background: Recently, cyclic diguanylate monophosphate (c-di-GMP) drug delivery has garnered interest due to its potential in cancer immune modulation. In this pilot study, we developed a novel c-di-GMP formulation based on peptide amyloids. The amyloid depots were formed by combining an amyloidogenic prone 12 amino acid peptide sequence of receptor-interacting protein kinase 3 (RIP3) with cationic lipid ALC-0315, or using lysozyme proteins. Both RIP3 and lysozyme proteins have intrinsic physiological functions. This is the first time intrinsic peptides/protein-based amyloids have been explored for c-di-GMP delivery. The main goal was to evaluate how these amyloid depots could enhance c-di-GMP drug delivery and modulate responses in RAW 264.7 macrophage-like cells. Methods: Physicochemical characterization and cellular assays were utilized to characterize the amyloid structures and assess the efficacy. Results: Our results show that amyloid aggregates significantly improve the therapeutic efficacy of c-di-GMP. When RAW 264.7 cells were treated with c-di-GMP amyloids, we observed at least a 1.5-fold change in IL-6 expression, nitric oxide (NO) production, and reactive oxygen species (ROS) production compared to treatment with 5x free c-di-GMP treatment, which suggests that this system holds promise for enhanced therapeutic effects. Conclusions: Overall, these findings emphasize the potential of amyloid-based delivery systems as a promising approach for c-di-GMP delivery, warranting further investigations into their potential in therapeutic applications. Full article
(This article belongs to the Special Issue Advances in Delivery of Peptides and Proteins)
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14 pages, 2594 KiB  
Article
Comparison of Drying Techniques to Produce Stable and Bioavailable Encapsulated ACE-2 Nanoparticles
by Yigong Guo, Alberto Baldelli, Dai Shi, David D. Kitts, Anubhav Pratap-Singh and Anika Singh
Pharmaceutics 2025, 17(4), 537; https://doi.org/10.3390/pharmaceutics17040537 - 21 Apr 2025
Viewed by 308
Abstract
Background/Objectives: COVID-19 infection continues globally, with frequent emergence of unfamiliar SARS-CoV-2 variants acting to impair immunity. The competitive binding of SARS-CoV-2 spike proteins and angiotensin-converting enzyme 2 (ACE-2) can decrease the binding of the virus on native ACE-2 receptors on healthy human cells. [...] Read more.
Background/Objectives: COVID-19 infection continues globally, with frequent emergence of unfamiliar SARS-CoV-2 variants acting to impair immunity. The competitive binding of SARS-CoV-2 spike proteins and angiotensin-converting enzyme 2 (ACE-2) can decrease the binding of the virus on native ACE-2 receptors on healthy human cells. It remains a practical approach to lessen viral spread. In this study, a method to encapsulate ACE-2 in the form of chitosan/tripolyphosphate cross-linked nanoparticles (NPs) was developed with emphasis placed on the best dehydration method to secure functional ACE-2 nanoparticles. Methods: Methods: Preparation conditions were assessed by varying pH (4.0–6.5) and the ratio between chitosan and ACE-2 mixing ratios (1:1, 1.5:1, 2:1, 2.5:1, and 3:1). The formulated NPs were then dehydrated using different approaches that included spray-drying (SD), freeze-drying (FD), and spray-freeze drying (SFD) and used varying mannitol concentrations (0, 1:1, and 5:1 of total weight). The mannitol was served as a cryoprotectant in this study. Results: The best formulation achieved used a pH 5.5 with a mixing chitosan–ACE-2 ratio of 2:1, where ACE-2-loaded NPs had an average particle size of 303.7 nm, polydispersity index (PDI) of 0.21, encapsulation efficiency (EE) of 98.4%, and ACE-2 loading content (LC) of 28.4%. After reconstitution, all SD samples had a relatively low yield rate, but the ACE-2 NPs dehydrated specifically using SFD required a lower amount of added mannitol (1:1 of its total weight) and produced a higher yield rate (p < 0.05) and similar PDI and EE values, along with relatively good particle size and LC. This formulation also produced a high ACE-2 release and uptake in differentiated Caco-2 cells, thus representing an effective ACE-2 encapsulation procedure for use with dry powders. Conclusions: This work showed that spray-freeze drying was the best method to dehydrate ACE-2 NPs, using less cryoprotectant to create a significant advantage in terms of greater loading capacity with lower additive requirements. Full article
(This article belongs to the Special Issue Advances in Delivery of Peptides and Proteins)
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29 pages, 6039 KiB  
Article
Innovative Solid Lipid Nanoparticle-Enriched Hydrogels for Enhanced Topical Delivery of L-Glutathione: A Novel Approach to Anti-Ageing
by Mengyang Liu, Manisha Sharma, Guoliang Lu, Zhiwen Zhang, Wenting Song and Jingyuan Wen
Pharmaceutics 2025, 17(1), 4; https://doi.org/10.3390/pharmaceutics17010004 - 24 Dec 2024
Cited by 2 | Viewed by 1143
Abstract
Background: Skin ageing, driven predominantly by oxidative stress from reactive oxygen species (ROS) induced by environmental factors like ultraviolet A (UVA) radiation, accounts for approximately 80% of extrinsic skin damage. L-glutathione (GSH), a potent antioxidant, holds promise in combating UVA-induced oxidative stress. However, [...] Read more.
Background: Skin ageing, driven predominantly by oxidative stress from reactive oxygen species (ROS) induced by environmental factors like ultraviolet A (UVA) radiation, accounts for approximately 80% of extrinsic skin damage. L-glutathione (GSH), a potent antioxidant, holds promise in combating UVA-induced oxidative stress. However, its instability and limited penetration through the stratum corneum hinder its topical application. This study introduces a novel solid lipid nanoparticle (SLN)-enriched hydrogel designed to enhance GSH stability, skin penetration, and sustained release for anti-ageing applications. Methods: GSH-loaded SLNs were prepared via a double-emulsion technique and optimized using factorial design. These SLNs were incorporated into 1–3% (w/v) Carbopol hydrogels to produce a semi-solid formulation. The hydrogel’s characteristics, including morphology, mechanical and rheological properties, drug release, stability, antioxidant activity, cytotoxicity, and skin penetration, were evaluated. Results: SEM and FTIR confirmed the uniform dispersion of SLNs within the hydrogel. The formulation exhibited desirable properties, including gel strength (5.1 ± 0.5 g), spreadability (33.6 ± 1.9 g·s), pseudoplasticity, and elasticity. In vitro studies revealed a biphasic GSH release profile, with sustained release over 72 h and over 70% cumulative release. The hydrogel significantly improved antioxidant capacity, protecting human fibroblasts from UVA-induced oxidative stress and enhancing cell viability. Stability studies indicated that 4 °C was optimal for storage over three months. Notably, the hydrogel enhanced GSH penetration through the stratum corneum by 3.7-fold. Conclusions: This SLN-enriched hydrogel effectively improves GSH topical delivery and antioxidant efficacy, providing a promising platform for anti-ageing and other bioactive compounds with similar delivery challenges. Full article
(This article belongs to the Special Issue Advances in Delivery of Peptides and Proteins)
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