Transdermal drug delivery provides a noninvasive route that avoids gastrointestinal degradation and hepatic first-pass metabolism, offering clinical advantages over some oral and injectable routes. However, broader application is constrained by the barrier function of the stratum corneum and by insufficient accumulation of therapeutic agents within target skin tissues. Metal-organic frameworks (MOFs) have attracted attention as platforms to address these limitations because of their distinctive structural and chemical properties.
MOFs are characterized by very large surface areas, tunable pore structures, and versatile surface chemistries that permit tailored interactions with drug molecules and biological interfaces. These material features underpin the potential of MOF-based constructs to improve transdermal transport and local therapeutic concentrations.
MOF-based transdermal systems offer several interrelated advantages relevant to topical and transdermal therapeutics:
High drug-loading capacity, which is especially valuable for hydrophobic compounds and large macromolecules that are otherwise challenging to deliver across skin.
Tunable porosity and surface chemistry that enable controlled and programmable multidrug delivery, allowing combination therapies or staged release profiles.
Favorable biocompatibility reported in the literature, supporting their use in contact with skin or wound tissue.
Capability to integrate diagnostic and therapeutic functions within a single platform, and to combine with complementary physical modalities (for example, adjunctive energy-based treatments) to create multifunctional systems.
These properties make MOFs promising carriers for a range of dermal and transdermal therapeutic goals.
Rational design of MOF-based transdermal platforms relies on controlling pore size, surface functionality, and overall architecture to influence drug loading, release kinetics, and skin interactions. The tunable pore structure determines which drug molecules can be encapsulated and how they are released, while surface modifications can improve compatibility with hydrophobic drugs or enhance interactions with skin lipids.
Mechanistic considerations relevant to transdermal efficacy include:
How MOF structure and surface chemistry influence penetration across the stratum corneum and retention in target skin layers.
The capacity for stimuli-responsive release (for example, triggered by pH, enzymes, or external stimuli) to achieve on-demand or spatially selective drug delivery.
Integration of diagnostic reporters or imaging agents within MOFs to enable theranostic approaches that combine monitoring and therapy.
The review synthesizes principles guiding these design decisions and highlights how MOF characteristics map to functional transdermal outcomes.
Recent advances in MOF-based transdermal systems have been explored across several biomedical areas:
Diabetic wound management: MOF platforms may support local delivery of antimicrobials, growth factors, or agents that modulate the wound environment to promote healing.
Skin regeneration: Controlled release of regenerative therapeutics from MOFs can potentially support tissue repair and remodeling.
Skin cancer therapy: Localized delivery strategies using MOFs aim to increase tumor-specific drug concentrations while limiting systemic exposure.
Cosmetic delivery: MOFs offer routes to load and release cosmetically active agents, including hydrophobic molecules, with improved stability and delivery profiles.
These application areas illustrate the breadth of MOF utility for both therapeutic and aesthetic skin-targeted interventions.
Despite promising preclinical advances, clinical translation of MOF-based transdermal systems faces several unresolved challenges noted by the authors:
Insufficient long-term biosafety evaluation. Comprehensive data on chronic exposure, immunogenicity, and local tissue responses are lacking.
Incomplete understanding of degradation behavior and systemic biodistribution of MOF materials after topical or transdermal use.
Limited manufacturing scalability. Production methods for complex multifunctional MOF constructs may not yet meet the scalability and reproducibility requirements for clinical-grade manufacturing.
Regulatory requirements for complex multifunctional systems present hurdles, given the combined-material, drug, and device aspects of many MOF platforms.
Addressing these challenges will be essential before widespread clinical adoption.
The review highlights opportunities provided by artificial intelligence (AI) to mitigate several translational barriers. Specific AI applications include:
Accelerating MOF design by predicting structure–property relationships, enabling faster identification of candidate frameworks with desired pore sizes, surface chemistries, and stability profiles.
Optimizing stimuli-responsive drug release profiles through in silico modeling, which can reduce experimental iterations when developing controlled-release formulations.
Supporting development of personalized transdermal therapies by integrating patient- and disease-specific parameters into design workflows to tailor release kinetics and dosing.
These AI-driven strategies could complement experimental work and help prioritize constructs for safety testing and scale-up.
The integrated perspective presented emphasizes design principles, therapeutic promise, and the practical barriers that must be overcome for clinical translation. Future work identified by the review centers on expanding long-term biosafety and degradation studies, elucidating biodistribution after topical application, improving manufacturing scalability and reproducibility, and engaging regulatory pathways for multifunctional systems.
AI is identified as a promising enabler to accelerate materials discovery, optimize functional performance, and support personalized approaches. Overall, MOF-based transdermal systems offer notable theoretical and preclinical advantages, but successful clinical development will require focused efforts on safety evaluation, scalable manufacturing, and regulatory strategy. Details beyond these high-level findings (such as specific experimental results, quantitative outcomes, or individual study protocols) were not reported in the source abstract.