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Pharmaceutics
Special Issues
Current and Future Perspectives in Dermal and Transdermal Drug Delivery
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Current and Future Perspectives in Dermal and Transdermal Drug Delivery

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

Deadline for manuscript submissions: 30 November 2026 | Viewed by 7118

Editors

Dr. Modestas Žilius

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Guest Editor
1. Institute of Pharmaceutical Technologies, Lithuanian University of Health Sciences, Sukileliu av. 13, LT-50162 Kaunas, Lithuania
2. Department of Clinical Pharmacy, Lithuanian University of Health Sciences, Sukileliu av. 13, LT-50162 Kaunas, Lithuania
Interests: dermatological products; design of experiments; in vitro release; ex vivo skin penetration; emulgels; hydrogels; polymeric films
Prof. Dr. Vitalis Briedis

E-Mail Website
Guest Editor
Department of Clinical Pharmacy, Lithuanian University of Health Sciences, Sukileliu av. 13, LT-50162 Kaunas, Lithuania
Interests: clinical pharmacy; biopharmaceutics; transdermal delivery; pharmaceutical biotechnology
Dr. Agnė Mazurkevičiūtė

E-Mail Website
Guest Editor Assistant
1. Institute of Pharmaceutical Technologies, Lithuanian University of Health Sciences, Sukileliu av. 13, LT-50162 Kaunas, Lithuania
2. Department of Clinical Pharmacy, Lithuanian University of Health Sciences, Sukileliu av. 13, LT-50162 Kaunas, Lithuania
Interests: dermatological products; rheology; in vitro release; ex vivo skin penetration

Special Issue Information

Dear Colleagues,

Dermal and transdermal drug delivery continue to evolve as pivotal strategies for both localized and systemic therapy, driven by advances in formulation science, device technologies, and translational research. This Special Issue aims to provide a comprehensive overview of current achievements while critically exploring future directions that will shape the next generation of skin-based therapeutics.

The collection will feature original research articles and authoritative reviews addressing innovative formulation approaches, including lipid- and polymer-based carriers, nanostructured systems, and prodrug strategies designed to overcome the skin barrier and optimize therapeutic performance. Emphasis will be placed on physical and device-assisted delivery technologies—microneedles, laser-assisted permeabilization, iontophoresis, and wearable platforms—that are redefining the possibilities of controlled and patient-centric drug administration.

Contributions will also highlight advances in predictive models for skin delivery, encompassing in vitro and ex vivo methodologies, in vitro–in vivo correlations, and emerging in silico and AI-driven tools that support rational product development. Finally, this Special Issue will address translational, regulatory, and manufacturing challenges, including Quality by Design, bioavailability and bioequivalence assessment, and pathways for clinical implementation.

By integrating fundamental science with applied innovation, this collection seeks to offer a forward-looking perspective on how dermal and transdermal drug delivery can meet future therapeutic, technological, and regulatory demands.

Subtopics of interest include:

  1. Advanced formulation strategies for dermal and transdermal delivery;
  2. Physical and device-assisted technologies for skin permeabilization;
  3. Targeted and precision delivery to skin and systemic circulation;
  4. In vitro, in vivo, and in silico models for predictive skin delivery.

Any research topic on emerging platforms for dermal and transdermal therapeutics will be considered.

Dr. Modestas Žilius
Prof. Dr. Vitalis Briedis
Guest Editors

Dr. Agnė Mazurkevičiūtė
Guest Editor Assistant

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 250 words) can be sent to the Editorial Office for assessment.

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

  • dermal/transdermal delivery
  • skin penetration/permeation
  • physical/targeted delivery
  • device technology
  • formulation approaches
  • predictive models

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Published Papers (6 papers)

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Research

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16 pages, 2712 KB  
Article
Meibomian Gland-Mediated Drug Delivery via Eyelid Application of Troxipide Nanoparticles Improves an N-Acetylcysteine-Induced Dry Eye
by Hiroko Otake, Rie Tanaka, Fumihiko Ogata, Manju Misra, Kazutaka Kanai, Masanobu Tsubaki, Naoki Yamamoto, Naohito Kawasaki and Noriaki Nagai
Pharmaceutics 2026, 18(8), 973; https://doi.org/10.3390/pharmaceutics18080973 - 8 Aug 2026
Viewed by 427
Abstract
Background/Objectives: Dry eye disease (DED) is a multifactorial disorder characterized by tear film instability, inflammation, and ocular surface damage, which significantly impairs visual function and quality of life. Conventional ophthalmic formulations, such as eye drops, have low bioavailability owing to rapid elimination, necessitating [...] Read more.
Background/Objectives: Dry eye disease (DED) is a multifactorial disorder characterized by tear film instability, inflammation, and ocular surface damage, which significantly impairs visual function and quality of life. Conventional ophthalmic formulations, such as eye drops, have low bioavailability owing to rapid elimination, necessitating frequent administration. In this study, we developed an eyelid-applied drug delivery system (DDS) based on troxipide (TRO) nanoparticle formulation (TRO-NP@EG) to achieve sustained ocular surface delivery. Methods: TRO nanosuspensions were prepared by wet bead milling and incorporated into a Carbopol-based gel. Particle size, dispersion stability, and uniformity were evaluated, and in vitro drug release studies was compared with that of TRO-MP@EG. In vivo drug transfer into tear fluid was assessed in rabbits following eyelid application, and therapeutic efficacy was evaluated in an N-acetylcysteine-induced dry eye model. Results: TRO nanosuspensions had a mean particle size of approximately 118 nm. TRO-NP@EG exhibited superior dispersion stability and uniformity and achieved 2.5-fold higher drug release than TRO-MP@EG, while the nanoparticles remained in solid form. In vivo studies in rabbits, TRO-NP@EG significantly enhanced drug transfer into tear fluid, primarily via the meibum pathway. Furthermore, TRO-NP@EG significantly improved mucin levels, tear secretion, and tear film stability compared with TRO-MP@EG in an N-acetylcysteine-induced dry eye model. Conclusions: These findings suggest that eyelid application of nanoparticle-based formulations enables efficient and sustained drug delivery to the ocular surface via the meibomian glands. Therefore, TRO-NP@EG represents a promising therapeutic strategy for DED, providing enhanced efficacy and a novel route of administration for ophthalmic DDSs. Full article
(This article belongs to the Special Issue Current and Future Perspectives in Dermal and Transdermal Drug Delivery)
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23 pages, 10628 KB  
Article
Design and Development of a Bioink for Fabricating Crosslinked Hydrogel Microneedles via 3D Printing for Transdermal Delivery of Estradiol Nanoparticles
by Southamany Sisavengsouk, Teeratas Kansom, Boonnada Pamornpathomkul, Porawan Aumklad, Tanasait Ngawhirunpat, Praneet Opanasopit and Phuvamin Suriyaamporn
Pharmaceutics 2026, 18(7), 772; https://doi.org/10.3390/pharmaceutics18070772 - 24 Jun 2026
Viewed by 841
Abstract
Background: Conventional transdermal drug delivery systems are often limited by poor skin permeability and low drug loading efficiency, necessitating the development of advanced delivery platforms. Objectives: This study aimed to develop and optimize photopolymerizable bioinks (PBs) for liquid crystal display (LCD)-based [...] Read more.
Background: Conventional transdermal drug delivery systems are often limited by poor skin permeability and low drug loading efficiency, necessitating the development of advanced delivery platforms. Objectives: This study aimed to develop and optimize photopolymerizable bioinks (PBs) for liquid crystal display (LCD)-based 3D printing of crosslinked hydrogel microneedles (cHMNs) to enhance transdermal delivery of estradiol valerate (E2V). Methods: A Box–Behnken design (BBD) was used to optimize the effects of Gantrez™ S-97, Jurymer™, and polyvinyl alcohol (PVA) on viscosity, exposure time, hardness, and elasticity, with strong predictive performance (R2 = 0.9702–0.9907). Results: Estradiol valerate-loaded nanoparticles (E2V-NPs) were prepared via ionotropic gelation, exhibiting a particle size of 698.33 (0.78) nm, PDI of 0.50 (0.06), zeta potential of −39.09 (7.32) mV, and high encapsulation efficiency (86.87 (0.78)%). The optimized PBs enabled fabrication of uniform cHMNs (~800 µm height) with adequate mechanical strength (hardness 20.45 (1.23) N; elasticity 2.97 (0.49) MPa) and effective insertion capability. The E2V-NPs-loaded cHMNs exhibited sustained drug release over 12 days (~56.92 (4.27)%). Skin permeation studies showed a significantly enhanced flux (10.81 (4.55) µg/cm2/h) and cumulative permeation (12.94 (2.06) µg/cm2) compared to topical E2V-NPs and suspension, along with increased skin accumulation (38.55 (0.10) µg). Cytotoxicity studies confirmed that E2V and E2V-NPs were biocompatible (>80% viability), while PBs showed concentration-dependent cytotoxicity. Conclusions: Overall, this integrated platform combining design of experiment, nanoparticles, microneedles, and LCD 3D printing offered a promising strategy for enhancing transdermal drug delivery efficiency and reproducibility. Full article
(This article belongs to the Special Issue Current and Future Perspectives in Dermal and Transdermal Drug Delivery)
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13 pages, 1125 KB  
Article
Modulation of Caffeine Permeation Kinetics in a Skin-PAMPA Model by Probiotic Lysates and Bile Acids
by Maja Đanić, Natalija Dedić, Dragana Zaklan, Slavica Lazarević, Bojan Stanimirov, Momir Mikov and Nebojša Pavlović
Pharmaceutics 2026, 18(6), 688; https://doi.org/10.3390/pharmaceutics18060688 - 31 May 2026
Viewed by 1038
Abstract
Background: Caffeine, although widely used in dermatological and cosmetic products, exhibits limited permeability through the stratum corneum, highlighting the need for strategies for optimizing delivery. The aim of this study was in vitro investigation of the effects of probiotic bacterial lysates and [...] Read more.
Background: Caffeine, although widely used in dermatological and cosmetic products, exhibits limited permeability through the stratum corneum, highlighting the need for strategies for optimizing delivery. The aim of this study was in vitro investigation of the effects of probiotic bacterial lysates and submicellar concentrations of bile acids on caffeine permeation, with a particular focus on permeation kinetics. Methods: Caffeine permeability was evaluated using the Skin Parallel Artificial Membrane Permeability Assay (Skin-PAMPA). Donor and acceptor concentrations were quantified by HPLC at predefined time points (1, 2, 4, 6, and 12 h), followed by calculation of apparent permeability coefficients, cumulative permeation profiles, and interval permeation rates in systems containing probiotic lysates and submicellar concentrations of cholic acid (CA) or deoxycholic acid (DCA). Results: Probiotic lysates significantly reduced caffeine permeability (0.98 ± 0.02 × 10−6 vs. 1.57 ± 0.14 × 10−6 cm/s in the control group) and modified transport kinetics resulting in lower early-phase interval permeation rates and reduced cumulative permeation. Conversely, bile acids increased the apparent permeability of caffeine, with the highest value observed in the DCA group (2.30 ± 0.08 × 10−6 cm/s). Conclusions: Overall, probiotic lysates and bile acids modulated caffeine permeation across the Skin-PAMPA membrane primarily by reshaping permeation kinetics rather than simply changing overall permeability. Their combined effects may provide a basis for designing topical formulations with tailored permeation profiles. Full article
(This article belongs to the Special Issue Current and Future Perspectives in Dermal and Transdermal Drug Delivery)
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23 pages, 13434 KB  
Article
Topical C-Phycocyanin-Loaded Transfersomes Attenuate Early Proinflammatory Epidermal Remodelling in a DMBA/TPA-Induced Mouse Model of Skin Dysplasia
by Daiva Galinytė, Nomeda Juodžiukynienė, Ingrida Balnytė, Vilma Zigmantaitė, Jūratė Karosienė, Jurga Bernatoniene and Nijolė Savickienė
Pharmaceutics 2026, 18(5), 600; https://doi.org/10.3390/pharmaceutics18050600 - 14 May 2026
Cited by 1 | Viewed by 1002
Abstract
Background/Objectives: Cutaneous squamous cell carcinoma (cSCC) develops through inflammation-driven preneoplastic alterations characterized by epidermal hyperplasia, dysplasia, and increased proliferative activity. C-phycocyanin (C-PC) possesses antioxidant and anti-inflammatory properties; however, its topical potential to attenuate a tumour-promoting cutaneous microenvironment is limited by poor skin [...] Read more.
Background/Objectives: Cutaneous squamous cell carcinoma (cSCC) develops through inflammation-driven preneoplastic alterations characterized by epidermal hyperplasia, dysplasia, and increased proliferative activity. C-phycocyanin (C-PC) possesses antioxidant and anti-inflammatory properties; however, its topical potential to attenuate a tumour-promoting cutaneous microenvironment is limited by poor skin penetration. This study evaluated the effects of C-PC-loaded transfersomes in a 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse model of skin carcinogenesis. Methods: Male BALB/c mice were assigned to six groups (n = 10 per group). Carcinogenesis was initiated with a single topical application of DMBA, followed by twice-weekly TPA application for 16 weeks. C-PC-loaded transfersomes (1 mg/mL or 10 mg/mL) were applied topically. Histopathological assessment included epidermal thickness, rete ridge depth, mitotic activity, mast cell density, and semi-quantitative scoring of hyperplasia, dysplasia, and inflammation. Ki-67 immunohistochemistry was used to evaluate basal and suprabasal proliferation. Results: Carcinogen exposure induced marked epidermal thickening, severe dysplasia, increased mitotic activity, elevated Ki-67 expression, and pronounced dermal inflammation. Treatment with C-PC-loaded transfersomes significantly reduced epidermal thickness, rete ridge depth, mast cell density, mitotic counts, and suprabasal Ki-67 index. The 1 mg/mL concentration demonstrated the most consistent attenuation of dysplasia severity and inflammatory changes. No adverse histopathological alterations were observed in internal organs. Conclusions: These findings indicate that transfersome-mediated topical delivery of C-PC attenuates early inflammation-driven epidermal remodelling and tumour-promoting alterations in experimental skin carcinogenesis, supporting its potential as a topical preventive strategy. Full article
(This article belongs to the Special Issue Current and Future Perspectives in Dermal and Transdermal Drug Delivery)
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Review

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56 pages, 9471 KB  
Review
Pharmacokinetic Relevance of In Vitro Skin Models: Absorption, Cutaneous Distribution, Metabolism, and Clearance-like Removal in Dermal and Transdermal Drug Testing
by Filip Dugonik, Urška Jeršič, Lejla Kač, Uroš Maver and Tina Maver
Pharmaceutics 2026, 18(9), 1152; https://doi.org/10.3390/pharmaceutics18091152 - 14 Sep 2026
Viewed by 117
Abstract
Background: In vitro skin models are widely used in dermal and transdermal drug development, yet their pharmacokinetic interpretation often remains endpoint-dependent and does not fully capture cutaneous disposition, including partitioning, local metabolism, or clearance-like removal. This review evaluates the utility of these [...] Read more.
Background: In vitro skin models are widely used in dermal and transdermal drug development, yet their pharmacokinetic interpretation often remains endpoint-dependent and does not fully capture cutaneous disposition, including partitioning, local metabolism, or clearance-like removal. This review evaluates the utility of these models through a comprehensive pharmacokinetic process framework. Methods: Using a structured literature search, we critically compared data from studies utilizing a range of in vitro skin models, including synthetic membranes, ex vivo human skin, reconstructed human epidermis, full-thickness equivalents, and advanced bioprinted or microfluidic platforms. The assessment focused on model performance across the key processes of absorption, distribution, metabolism, and elimination. Results: Our analysis reveals that alternative barriers exhibit no uniform direction of bias relative to human skin; model rank order varies with compound, formulation, and dose, so that the available evidence does not currently support a single universal scaling relationship, although calibration within a defined applicability domain may remain possible. Synthetic membranes provide reproducible platforms for formulation ranking but lack biological retention and metabolism. Ex vivo human skin remains the closest reference for permeation and mass balance, though donor variability and storage sensitivity limit standardization. Reconstructed epidermis supports standardized permeation and epidermal targeting, while full-thickness equivalents permit dermal retention analysis. Advanced perfused constructs extend experimental capabilities, but their predictive performance remains largely uncharacterized. Conclusions: No single model universally replicates human pharmacokinetics. Model selection must therefore be carefully aligned with the specific pharmacokinetic process of interest, the model’s biological capacity, and the intended context of use to ensure clinically relevant data interpretation. Full article
(This article belongs to the Special Issue Current and Future Perspectives in Dermal and Transdermal Drug Delivery)
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49 pages, 4850 KB  
Review
Ultradeformable Vesicles for Wound Healing: Ethosomes, Transferosomes, and Transethosomes in Topical Drug Delivery
by Shery Jacob, Namitha Raichel Varkey and Anroop B. Nair
Pharmaceutics 2026, 18(3), 361; https://doi.org/10.3390/pharmaceutics18030361 - 13 Mar 2026
Cited by 11 | Viewed by 2865
Abstract
Wound healing is a dynamic and multifaceted biological process involving hemostasis, inflammation, proliferation, and tissue remodeling. Topical therapy is widely preferred for wound management due to its localized action and reduced systemic adverse effects. However, the effective delivery of therapeutic agents is often [...] Read more.
Wound healing is a dynamic and multifaceted biological process involving hemostasis, inflammation, proliferation, and tissue remodeling. Topical therapy is widely preferred for wound management due to its localized action and reduced systemic adverse effects. However, the effective delivery of therapeutic agents is often limited by the skin’s barrier properties, the complex wound microenvironment, and the physicochemical characteristics of drugs. This review highlights the key physicochemical parameters governing topical drug delivery in wound therapy, including drug solubility, molecular size, lipophilicity, vesicle size distribution, surface charge, encapsulation efficiency, lipid composition, ethanol concentration, and vesicle deformability, which collectively influence drug permeation and retention at the wound site. Nanovesicular delivery systems have emerged as promising strategies to overcome these limitations. In particular, ultradeformable vesicles such as ethosomes, transferosomes, and transethosomes have demonstrated enhanced skin permeation and improved drug deposition in periwound tissue due to their flexible membrane structure and optimized physicochemical properties. This review systematically discusses the composition, preparation techniques, and critical formulation parameters of these vesicular systems that determine their stability, elasticity, and permeation performance. Furthermore, their applications in delivering anti-inflammatory drugs, antimicrobial agents, bioactive phytochemicals, and regenerative therapeutics for different wound types are examined. Widely used in vitro, ex vivo, and in vivo evaluation methods, including permeation studies and wound healing models such as excision, burn, infected, and diabetic wounds, are also summarized. Finally, the review outlines current challenges related to formulation standardization, physicochemical characterization, safety assessment, and large-scale production, while highlighting the future potential of ultradeformable vesicles as next-generation nanocarriers for advanced wound healing therapies. Full article
(This article belongs to the Special Issue Current and Future Perspectives in Dermal and Transdermal Drug Delivery)
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