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Pharmaceutics
Special Issues
Advanced Drug Delivery Systems for Enhanced Transdermal and Dermal Delivery
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Advanced Drug Delivery Systems for Enhanced Transdermal and Dermal Delivery

A Special Issue of Pharmaceutics (ISSN 1999-4923) belonging to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: 31 October 2026 | Viewed by 3109

Editors

Dr. Siyuan Chen

E-Mail Website
Guest Editor
College of Materials Science and Engineering, Nanjing Tech University, Nanjing 211816, China
Interests: skin inflammation; hyaluronan; skin barrier; microneedle; skin microbiota; transdermal delivery; nano-drug delivery system
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Jinbing Xie

E-Mail Website
Guest Editor
Medical School, Southeast University, Nanjing, China
Interests: biomaterials; biomedical engineering
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue addresses developments in engineered drug delivery systems designed to overcome the skin's formidable barrier for therapeutic and cosmetic purposes. While drug delivery systems are a pivotal innovation, this collection expands the horizon to encompass a broader spectrum of cutting-edge strategies. This includes, but is not limited to, hydrogels, lipid-based, polymeric, and inorganic micro- and nano-particulate systems, microneedles, ionic liquids, and novel emulsion technologies. This issue aims to highlight the convergence of material science, pharmaceutical technology, and dermatology in the creation of next-generation delivery platforms. We welcome contributions that explore the design, characterization, and mechanistic understanding of skin penetration, including preclinical/clinical evaluations of these systems. A particular focus is targeted delivery for treating skin diseases (e.g., psoriasis, melanoma, infections), enabling systemic administration via the transdermal route, and advancing cosmetic and dermatological formulations. By providing a platform for diverse yet focused research, this Special Issue will chart the future of cutaneous drug delivery, emphasizing efficacy, safety, patient compliance, and translational potential. We invite researchers to submit original research articles and comprehensive reviews across related disciplines.

Dr. Siyuan Chen
Prof. Dr. Jinbing Xie
Guest Editors

Manuscript Submission Information

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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-anonymized 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

  • cutaneous drug delivery
  • transdermal delivery
  • skin penetration
  • advanced delivery systems
  • micro- and nanocarriers
  • microneedles
  • dermatological applications

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Published Papers (4 papers)

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Research

24 pages, 8619 KB  
Article
A Hyaluronic Acid-Coated Ethosomal Delivery System for Improving the Topical Delivery of Glycyrrhetinic Acid in Sensitive Skin
by Yuling Wang, Shujing Ren, Jun Deng, Dan Luo, Rui Liu, Yu Zhou, Siyuan Chen and Wei Liu
Pharmaceutics 2026, 18(9), 1114; https://doi.org/10.3390/pharmaceutics18091114 - 4 Sep 2026
Viewed by 346
Abstract
Background: Effective topical management of sensitive skin remains challenging because inadequate cutaneous delivery limits the therapeutic performance of many anti-inflammatory agents. Glycyrrhetinic acid (GA) possesses well-recognized anti-inflammatory and barrier-protective activities, yet its clinical potential is constrained by poor aqueous solubility and inefficient skin [...] Read more.
Background: Effective topical management of sensitive skin remains challenging because inadequate cutaneous delivery limits the therapeutic performance of many anti-inflammatory agents. Glycyrrhetinic acid (GA) possesses well-recognized anti-inflammatory and barrier-protective activities, yet its clinical potential is constrained by poor aqueous solubility and inefficient skin delivery. This study aimed to develop a hyaluronic acid (HA)-engineered ethosomal system to enhance the local delivery and therapeutic efficacy of GA for sensitive skin. Methods: HA-coated GA-loaded ethosomes (HAGA-ETs) were prepared by electrostatic adsorption of HA onto a cationic ethosomal template. The physicochemical properties, release behavior, storage stability, skin retention, cellular uptake, and biological activities of HAGA-ETs were systematically evaluated using TNF-α/IFN-γ-stimulated HaCaT cells and an SLS-induced 3D reconstructed skin model. Results: HAGA-ETs exhibited a mean particle size of 140.1 nm, encapsulation efficiency exceeding 95%, sustained drug release, and good storage stability. Compared with Free-GA and unmodified ethosomes, HAGA-ETs showed improved cytocompatibility, enhanced skin retention, greater keratinocyte uptake, and stronger anti-inflammatory activity. HA pre-saturation attenuated the enhanced cellular uptake of HAGA-ETs, supporting the involvement of HA receptor-mediated cellular interaction. HAGA-ETs also more effectively restored barrier-related markers, suppressed hyper-reactivity- and allergy-associated mediators, and inhibited the activation of MAPK/NF-κB, JAK1/STAT1, and TRPV1-related signaling pathways in both cellular and 3D skin models. Conclusions: HA surface engineering effectively improved the topical delivery and local therapeutic efficacy of GA by enhancing skin retention and keratinocyte interaction. HAGA-ETs represent a promising nanoplatform for the local management of sensitive skin. Full article
(This article belongs to the Special Issue Advanced Drug Delivery Systems for Enhanced Transdermal and Dermal Delivery)
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14 pages, 9591 KB  
Article
Radiofrequency Microporation Enhances Topical Minoxidil Delivery and Hair Regeneration in Androgenetic Alopecia
by Na-Young Yu, Kyu-Jin Cho, Saeeun Ryu, Gyulim Kim, Jae-Woo Shin, Donghee Park, Jongho Won, Young-Kee Shin, Eun-Ah Kim, Sang-Goo Cho, Nae-Won Kang, Byung-Hoon Lee, Nam-Young Kim, Eun-Seong Kim and Dae-Duk Kim
Pharmaceutics 2026, 18(9), 1081; https://doi.org/10.3390/pharmaceutics18091081 - 28 Aug 2026
Viewed by 476
Abstract
Background/Objectives: Androgenetic alopecia (AGA) is the most prevalent form of hair loss. Although topical minoxidil (MNX) is widely used to treat AGA, its efficacy is limited by poor penetration across the stratum corneum. This study evaluated radiofrequency (RF) microporation as a means [...] Read more.
Background/Objectives: Androgenetic alopecia (AGA) is the most prevalent form of hair loss. Although topical minoxidil (MNX) is widely used to treat AGA, its efficacy is limited by poor penetration across the stratum corneum. This study evaluated radiofrequency (RF) microporation as a means of enhancing cutaneous MNX delivery and hair-regrowth efficacy in a dihydrotestosterone (DHT)-induced AGA mouse model. Methods: RF-induced skin permeabilization and barrier recovery were assessed in rats using methylene blue and rhodamine B staining. In vivo skin deposition and pharmacokinetic studies were conducted to quantify cutaneous MNX accumulation and systemic exposure. Hair-regrowth efficacy was evaluated in DHT-treated mice. Results: RF microporation generated transient microchannels in the stratum corneum, increased rhodamine B penetration into deeper skin layers, and allowed substantial barrier recovery within 24 h. RF pretreatment significantly increased MNX deposition in the epidermis/dermis by 2.40-fold at 1 h and 1.94-fold at 3 h compared with topical MNX alone. RF-assisted topical administration resulted in a relative bioavailability of 11.17%, compared with 4.74% for topical administration without RF, while dose-normalized systemic exposure remained substantially lower than that following oral administration. In the AGA model, RF-assisted MNX treatment significantly increased hair coverage, length, and shaft thickness. Histological analysis further showed more prominent follicular structures in the RF-assisted MNX groups. Conclusions: RF microporation creates transient microchannels that enhance cutaneous MNX delivery and improve hair-regrowth efficacy. Importantly, RF-assisted topical administration maintained substantially lower systemic exposure than oral administration, supporting its potential as a needle-free strategy for topical AGA therapy and further translational evaluation. Full article
(This article belongs to the Special Issue Advanced Drug Delivery Systems for Enhanced Transdermal and Dermal Delivery)
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25 pages, 1032 KB  
Article
Mucoadhesive Nanostructured Lipid Carriers of Ketoconazole for Enhanced Dermal Delivery and Antifungal Activity: Formulation Optimization and In Vivo Evaluation
by Mashan Almutairi, Ahmed Adel Ali Youssef, Yazed S. Alsowaida, Ahmed Alobaida and Samir A. Ross
Pharmaceutics 2026, 18(6), 753; https://doi.org/10.3390/pharmaceutics18060753 - 19 Jun 2026
Viewed by 770
Abstract
Background/Objective: Topical therapy remains a cornerstone in managing fungal infections due to the deep-seated nature of the pathogens and the persistence of the disease. Ketoconazole (KTZ) is a broad-spectrum antifungal agent, but its highly lipophilic nature presents considerable challenges in developing effective topical [...] Read more.
Background/Objective: Topical therapy remains a cornerstone in managing fungal infections due to the deep-seated nature of the pathogens and the persistence of the disease. Ketoconazole (KTZ) is a broad-spectrum antifungal agent, but its highly lipophilic nature presents considerable challenges in developing effective topical formulations. Additionally, oral KTZ has been subject to labeling restrictions and market withdrawal due to its association with severe hepatic adverse effects. This study was conducted to design, optimize, and evaluate KTZ-loaded nanolipid carriers (NLCs; KTZ-NLCs) as a delivery platform that could improve cutaneous bioavailability and enhance antifungal activity. Methods: The optimized KTZ-NLCs were further incorporated into a mucoadhesive system (KTZ-NLCs-C) through the inclusion of Carbopol® 940 NF, aiming to improve the retention of the formulation on the skin surface. NLCs were characterized in terms of their physical appearance, particle size, polydispersity index, zeta potential, pH, viscosity, drug content, and entrapment efficiency. The optimized KTZ-NLC and KTZ-NLCs-C formulations were subsequently assessed for in vitro drug release, ex vivo skin permeation and deposition, as well as in vivo skin irritation. Results: In vitro release studies revealed that nanocarrier systems provided a sustained release of KTZ over 24 h. The ex vivo transdermal flux and permeability coefficient of KTZ from the lead KTZ-NLCs-C formulation were approximately 2.8-fold greater than those achieved with the marketed cream formulation. The in vivo skin irritation studies indicate that NLC-based formulations are suitable for topical applications. The lead formulation was stable for 90 days (the final time point evaluated) under refrigerated and room-temperature storage conditions. Conclusions: These findings suggest that the NLC-based system is a promising platform for the topical delivery of KTZ and has the potential to enhance the therapeutic outcomes for patients with superficial fungal infections. Full article
(This article belongs to the Special Issue Advanced Drug Delivery Systems for Enhanced Transdermal and Dermal Delivery)
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25 pages, 1344 KB  
Article
Ketoconazole-Loaded Mucoadhesive Nanoemulsions for the Better Management of Topical Fungal Infections: Optimization, In Vitro, Ex Vivo, and In Vivo Assessments
by Mashan Almutairi, Ahmed Adel Ali Youssef, Gehad M. Subaiea, Ahmed Alobaida and Sultan Almuntashiri
Pharmaceutics 2026, 18(5), 612; https://doi.org/10.3390/pharmaceutics18050612 - 17 May 2026
Cited by 1 | Viewed by 1001
Abstract
Background/Objective: The introduction of Ketoconazole (KZ, Nizoral®) in 1977 by Janssen Pharmaceutica marked a significant milestone in medical mycology as the first broad-spectrum oral antifungal agent. However, KZ is a highly lipophilic compound, presenting significant challenges in the development of efficient [...] Read more.
Background/Objective: The introduction of Ketoconazole (KZ, Nizoral®) in 1977 by Janssen Pharmaceutica marked a significant milestone in medical mycology as the first broad-spectrum oral antifungal agent. However, KZ is a highly lipophilic compound, presenting significant challenges in the development of efficient topical formulations. Moreover, oral KZ has undergone labeling revisions and market withdrawal due to serious hepatic side effects. This study aimed to design, optimize, and evaluate KZ-loaded nanoemulsions (NEs; KZ-NEs) as a delivery platform that could improve skin bioavailability and antifungal activity. Methods: Optimized KZ-NEs were converted to a mucoadhesive formulation (KZ-NEC) by the addition of Carbopol® 940 NF to enhance the adherence of the formulations to the skin surface. NEs were evaluated concerning physical appearance, globule size, polydispersity index, zeta potential, pH, viscosity, and drug content. Optimized KZ-NE and lead KZ-NEC formulations were further evaluated for in vitro release, ex vivo skin permeation and deposition, skin irritation, and in vivo studies. Results: In vitro release studies revealed that nanocarrier systems provided a sustained release of KZ over 24 h. The ex vivo permeability coefficients of KZ from the optimized KZ-NE and lead KZ-NEC formulations were approximately four- and three-fold greater than that achieved with the marketed cream formulation, respectively. In addition, the Cmax of the lead KZ-NEC formulation (14.4 ± 1.1 μg/mL) was significantly higher (p < 0.05) compared with the marketed cream formulation (10.5 ± 0.5 μg/mL). Moreover, in vitro antifungal susceptibility testing showed that KZ demonstrated improved antifungal efficacy when incorporated into the KZ-NE and KZ-NEC formulations. Neither of the NE-based formulations caused any alterations in skin color or morphology during the 24 h visual observation period. Both NE-based formulations were stable for 90 days (the last time-point tested) at three different storage conditions. Conclusions: NE-based formulation could serve as an effective topical delivery platform for KZ and could improve therapeutic outcomes for patients with topical fungal infections. Full article
(This article belongs to the Special Issue Advanced Drug Delivery Systems for Enhanced Transdermal and Dermal Delivery)
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