Transdermal Drug Delivery Systems and Technologies

Transdermal drug delivery systems (TDDS) provide a non-invasive route for systemic and local administration of therapeutic agents by traversing the skin’s outer barrier. Traditional first-generation patches rely on passive diffusion through the stratum corneum and are limited to small, lipophilic molecules. Second-generation approaches employ chemical enhancers, iontophoresis, ultrasound or thermal methods to perturb barrier lipids and improve permeation. The emergence of third-generation technologies, notably microneedle arrays, electroporation and laser-assisted delivery, has dramatically expanded the scope to include macromolecules, vaccines and even cell-based therapies. Microneedle platforms, fabricated from biodegradable polymers, metals or ceramics, may be solid, hollow, dissolving or hydrogel-forming, and can be engineered for sustained, pulsatile or on-demand release. Advances in materials science, microfabrication and bioconjugation have enabled the integration of nanoparticles, growth factors and sensors into TDDS for combined therapeutic delivery and real-time monitoring. Recent work has also explored the sampling and analysis of interstitial fluid to allow point-of-care pharmacokinetic profiling. Clinical translation has begun for hormone replacement, pain management, vaccination and chronic disease management, with several products approved and many in late-stage trials. The global impact of TDDS spans improved patient adherence, reduced healthcare costs and decentralised treatment paradigms, positioning transdermal technologies as a vital component of personalised medicine and public health strategies.

Research from Nature Portfolio

Recent studies have advanced the utility of dermal interstitial fluid (ISF) not only for diagnostic sensing but also for therapeutic monitoring. Novel microlitre-scale sampling techniques combined with miniaturised electrochemical and optical biosensors now enable continuous measurement of small-molecule drug concentrations and biomarkers directly within the dermis. These developments address the dynamic interplay between ISF, blood and lymph pressures, mitigate inflammation-induced artefacts and improve temporal resolution of pharmacokinetic profiles. This platform has shown particular promise for monitoring immunosuppressants, antidiabetic agents and chemotherapeutics, facilitating adaptive dosing regimens and personalised therapy outside of clinical settings.

Transdermal Drug Delivery Systems and Technologies publication trend

The graph below shows the total number of articles in transdermal drug delivery systems and technologies across all publications each year (not limited to Nature Index journals).

Technical terms

Stratum corneum: The outermost layer of the epidermis composed of dead keratinocytes and intercellular lipids, serving as the principal barrier to transdermal permeation.
Transdermal drug delivery system (TDDS): A formulation or device designed to transport active pharmaceutical ingredients across the skin into systemic circulation or local tissues.
Microneedles: Micron-scale projections engineered to painlessly breach the stratum corneum, creating transient conduits for drug transport.
Hydrogel-forming microneedles: Crosslinked polymer networks that swell upon skin insertion, forming continuous fluidic pathways between a drug reservoir and dermal microcirculation.
Interstitial fluid (ISF): The extracellular fluid in the dermal matrix, which can be sampled or sensed for biomarkers and drug concentrations.
Nanoparticles: Submicron carriers utilising lipids, polymers or inorganic matrices to encapsulate, protect and control the release of therapeutic agents.

References

1. Advances in Polysaccharide-Based Microneedle Systems for the Treatment of Ocular Diseases. Nano-Micro Letters (2024).
2. Opportunities and challenges in the diagnostic utility of dermal interstitial fluid. Nature Biomedical Engineering (2023).
3. Hydrogel forming microneedles loaded with VEGF and Ritlecitinib/polyhydroxyalkanoates nanoparticles for mini-invasive androgenetic alopecia treatment. Bioactive Materials (2024).
4. Enhancement strategies for transdermal drug delivery systems: current trends and applications. Drug Delivery and Translational Research (2021).
5. Recent advances in transdermal drug delivery systems: a review. Biomaterials Research (2021).