---
title: "MOF-Based Transdermal Drug Delivery: Mechanisms, Applications, and Translational Challenges"
id: "pubmed-42763813"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42763813"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42763813/"
doi: "10.1007/s41061-026-00566-8"
published_at: "2026-09-20T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# MOF-Based Transdermal Drug Delivery: Mechanisms, Applications, and Translational Challenges
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42763813
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42763813/)
- **DOI:** [10.1007/s41061-026-00566-8](https://doi.org/10.1007%2Fs41061-026-00566-8)
- **Published At:** 2026-09-20T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Transdermal delivery bypasses gastrointestinal degradation and hepatic first-pass metabolism, but is limited by the **stratum corneum** barrier and inadequate drug accumulation in target tissues. - **Metal-organic frameworks (MOFs)** are emerging as transdermal platforms due to high surface area, tunable pore structures, and adaptable surface chemistry. - MOF advantages include **high drug-loading capacity** (notably for hydrophobic compounds and macromolecules), programmable multidrug release, and generally favorable biocompatibility. - MOFs enable integration of diagnostic and therapeutic functions and can be combined with complementary physical treatment modalities for multifunctional transdermal systems. - Reported biomedical applications span diabetic wound management, skin regeneration, skin cancer therapy, and cosmetic delivery. - Major barriers to clinical translation are insufficient long-term biosafety data, incomplete understanding of MOF degradation and biodistribution, limited scalability of manufacturing, and regulatory complexity for multifunctional systems. - Recent advances in **AI** offer opportunities to accelerate MOF design, predict structure–property relationships, optimize stimuli-responsive release, and support development of personalized transdermal therapies. - The review synthesizes design principles, therapeutic applications, and translational challenges while outlining future directions for clinical development of MOF-based transdermal systems.
## Clinical Analysis & Structured Key Points
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Affiliations Expand ### Affiliations * 1 School of Food and Pharmaceutical Engineering, Zhaoqing University, Zhaoqing, 526061, People's Republic of China. * 2 Dongguan Key Laboratory of Drug Design and Formulation Technology, School of Pharmacy, Guangdong Medical University, Dongguan, 523808, People's Republic of China. * 3 Chemistry Department, Institute of Natural, Chemical, and Pharmaceutical Materials, Shahreza Campus, Islamic Azad University, Shahreza, Islamic Republic of Iran. * 4 School of Chemistry and Environmental Engineering, Sichuan University of Science and Engineering, Zigong, 643000, People's Republic of China. * 5 Dongguan Key Laboratory of Skin Health and Cosmetic Formulations, The Sixth People's Hospital of Dongguan, Dongguan, 523000, People's Republic of China. * 6 Dongguan Key Laboratory of Skin Health and Cosmetic Formulations, The Sixth People's Hospital of Dongguan, Dongguan, 523000, People's Republic of China. zhuangshuze@126.com. # Contributed equally. * PMID: **42763813** * DOI: [ 10.1007/s41061-026-00566-8 ](https://doi.org/10.1007/s41061-026-00566-8) Item in Clipboard Review # Advances in MOF-Based Transdermal Drug Delivery Systems: Mechanisms, Applications, and Future Prospects Deyun Ma et al. Top Curr Chem (Cham). 2026. Show details Display options Display options Format Abstract PubMed PMID Top Curr Chem (Cham) Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Top+Curr+Chem+%28Cham%29%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Top+Curr+Chem+%28Cham%29%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42763813/) . 2026 Sep 20;384(4):32. doi: 10.1007/s41061-026-00566-8. ### Authors [Deyun Ma](https://pubmed.ncbi.nlm.nih.gov/?term=Ma+D&cauthor_id=42763813)[#](https://pubmed.ncbi.nlm.nih.gov/42763813/#short-view-equal-contrib-explanation "Contributed equally")[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42763813/#short-view-affiliation-1 "School of Food and Pharmaceutical Engineering, Zhaoqing University, Zhaoqing, 526061, People's Republic of China."), [Sirui Guo](https://pubmed.ncbi.nlm.nih.gov/?term=Guo+S&cauthor_id=42763813)[#](https://pubmed.ncbi.nlm.nih.gov/42763813/#short-view-equal-contrib-explanation "Contributed equally")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42763813/#short-view-affiliation-2 "Dongguan Key Laboratory of Drug Design and Formulation Technology, School of Pharmacy, Guangdong Medical University, Dongguan, 523808, People's Republic of China."), [Ruohan Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+R&cauthor_id=42763813)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42763813/#short-view-affiliation-2 "Dongguan Key Laboratory of Drug Design and Formulation Technology, School of Pharmacy, Guangdong Medical University, Dongguan, 523808, People's Republic of China."), [Yingzi Feng](https://pubmed.ncbi.nlm.nih.gov/?term=Feng+Y&cauthor_id=42763813)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42763813/#short-view-affiliation-2 "Dongguan Key Laboratory of Drug Design and Formulation Technology, School of Pharmacy, Guangdong Medical University, Dongguan, 523808, People's Republic of China."), [Alireza Nezamzadeh-Ejhieh](https://pubmed.ncbi.nlm.nih.gov/?term=Nezamzadeh-Ejhieh+A&cauthor_id=42763813)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42763813/#short-view-affiliation-3 "Chemistry Department, Institute of Natural, Chemical, and Pharmaceutical Materials, Shahreza Campus, Islamic Azad University, Shahreza, Islamic Republic of Iran."), [Lu Lu](https://pubmed.ncbi.nlm.nih.gov/?term=Lu+L&cauthor_id=42763813)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42763813/#short-view-affiliation-4 "School of Chemistry and Environmental Engineering, Sichuan University of Science and Engineering, Zigong, 643000, People's Republic of China."), [Ying Pan](https://pubmed.ncbi.nlm.nih.gov/?term=Pan+Y&cauthor_id=42763813)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42763813/#short-view-affiliation-5 "Dongguan Key Laboratory of Skin Health and Cosmetic Formulations, The Sixth People's Hospital of Dongguan, Dongguan, 523000, People's Republic of China."), [Shuze Zhuang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhuang+S&cauthor_id=42763813)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42763813/#short-view-affiliation-6 "Dongguan Key Laboratory of Skin Health and Cosmetic Formulations, The Sixth People's Hospital of Dongguan, Dongguan, 523000, People's Republic of China. zhuangshuze@126.com.") ### Affiliations * 1 School of Food and Pharmaceutical Engineering, Zhaoqing University, Zhaoqing, 526061, People's Republic of China. * 2 Dongguan Key Laboratory of Drug Design and Formulation Technology, School of Pharmacy, Guangdong Medical University, Dongguan, 523808, People's Republic of China. * 3 Chemistry Department, Institute of Natural, Chemical, and Pharmaceutical Materials, Shahreza Campus, Islamic Azad University, Shahreza, Islamic Republic of Iran. * 4 School of Chemistry and Environmental Engineering, Sichuan University of Science and Engineering, Zigong, 643000, People's Republic of China. * 5 Dongguan Key Laboratory of Skin Health and Cosmetic Formulations, The Sixth People's Hospital of Dongguan, Dongguan, 523000, People's Republic of China. * 6 Dongguan Key Laboratory of Skin Health and Cosmetic Formulations, The Sixth People's Hospital of Dongguan, Dongguan, 523000, People's Republic of China. zhuangshuze@126.com. # Contributed equally. * PMID: **42763813** * DOI: [ 10.1007/s41061-026-00566-8 ](https://doi.org/10.1007/s41061-026-00566-8) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract Transdermal drug delivery offers a noninvasive alternative to conventional administration by avoiding gastrointestinal degradation and hepatic first-pass metabolism. However, its broader clinical application remains limited by the barrier function of the stratum corneum and insufficient drug accumulation within target tissues. Metal-organic frameworks (MOFs), characterized by their high surface area, tunable pore structures, and versatile surface chemistry, have recently emerged as promising platforms for transdermal drug delivery. This review summarizes the key advantages of MOF-based transdermal systems, including high drug-loading capacity, particularly for hydrophobic compounds and macromolecules, programmable multidrug delivery, favorable biocompatibility, and the integration of diagnostic and therapeutic functions with complementary physical treatment modalities. We further discuss recent advances in the rational design of MOF-based transdermal platforms across major biomedical applications, including diabetic wound management, skin regeneration, skin cancer therapy, and cosmetic delivery. Despite these advances, clinical translation remains challenged by insufficient long-term biosafety evaluation, incomplete understanding of degradation behavior and biodistribution, limited manufacturing scalability, and regulatory requirements for complex multifunctional systems. Recent developments in artificial intelligence (AI) provide new opportunities to address several of these challenges by accelerating MOF design, predicting structure-property relationships, optimizing stimuli-responsive drug release, and supporting the development of personalized transdermal therapies. Overall, this review provides an integrated perspective on the design principles, therapeutic applications, and translational challenges of MOF-based transdermal systems, while outlining future directions for their successful clinical development. **Keywords:** AI; MOF; Therapeutic strategies; Transdermal delivery system. © 2026. The Author(s), under exclusive licence to Springer Nature Switzerland AG. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declarations. Conflict of Interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ## References 1. 1. Zgair A, Dawood Y, Ibrahem SM, Back H, Kagan L, Gershkovich P, Lee JB (2020) Predicting intestinal and hepatic first-pass metabolism of orally administered testosterone undecanoate. Appl Sci (Basel) 10:7283 - [DOI](https://doi.org/10.3390/app10207283) 2. 1. Xie L, Diao Z, Xia J, Zhang J, Xu Y, Wu Y, Liu Z, Jiang C, Peng Y, Song Z, Wang G, Zhu J, Sun J (2023) Comprehensive evaluation of metabolism and the contribution of the hepatic first-pass effect in the bioavailability of glabridin in rats. J Agric Food Chem 71:1944–1956 - [PubMed](https://pubmed.ncbi.nlm.nih.gov/36649475/) - [DOI](https://doi.org/10.1021/acs.jafc.2c06460) 3. 1. Wu Z, Zhang Y, Nie G, Liu J, Mei H, He Z, Douc P, Wang K (2022) Tracking the gastrointestinal digestive and metabolic behaviour of Dendrobium officinale polysaccharides by fluorescent labelling. Food Funct 13:7274 - [PubMed](https://pubmed.ncbi.nlm.nih.gov/35726749/) - [DOI](https://doi.org/10.1039/d2fo01506d) 4. 1. Roberts MS, Cheruvu HS, Mangion SE, Alinaghi A, Benson HAE, Mohammed Y, Holmes A, Hoek J, Pastore M, Grice JE (2021) Topical drug delivery: history, percutaneous absorption, and product development. Adv Drug Deliver Rev 177:113929 - [DOI](https://doi.org/10.1016/j.addr.2021.113929) 5. 1. Wong WF, Ang KP, Sethi G, Looi CY (2023) Recent advancement of medical patch for transdermal drug delivery. Medicina 59:778 - [PubMed](https://pubmed.ncbi.nlm.nih.gov/37109736/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/10142343/) - [DOI](https://doi.org/10.3390/medicina59040778) Show all 105 references ## Publication types * Review Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Review%22%5Bpt%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Review) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42763813/) ## MeSH terms * Administration, Cutaneous Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Administration%2C+Cutaneous%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Administration%2C+Cutaneous) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42763813/) * Animals Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Animals%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Animals) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42763813/) * Drug Carriers* / chemistry Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Drug+Carriers%2Fchemistry%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Drug+Carriers) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42763813/) * Drug Delivery Systems* Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.n
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