Advances in Nanocarrier Systems for Dermatologic Transdermal Drug Delivery: A Chemical and Molecular Review

Background: Transdermal drug delivery faces significant barriers due to the physicochemical properties of the stratum corneum, limiting the passive diffusion of therapeutic agents. Nanocarrier systems, including liposomes, ethosomes, niosomes, and polymeric nanoparticles, are being extensively investigated as innovative platforms to overcome these limitations in dermatologic applications. Objective: This review synthesizes recent advances in the molecular design of nanocarrier systems engineered for enhanced transdermal drug delivery, emphasizing critical chemical principles that underpin their development and optimization. Methods/Discussion: A targeted literature review was conducted using PubMed, Scopus, and Web of Science databases, identifying studies published between January 2023 and April 2025. A total of 64 peer-reviewed papers were selected based on relevance to nanocarrier-based dermatologic delivery systems. The included studies were analyzed for trends in particle size optimization, surface charge modulation (zeta potential), lipid phase behavior, PEGylation, surfactant composition, and pHresponsive or enzyme-cleavable linker strategies. Applications covered include nanocarrier-mediated delivery of tacrolimus and vitamin D3 for atopic dermatitis; methotrexate, calcipotriol, and siRNA for psoriasis; 5-fluorouracil and imiquimod for actinic keratosis and superficial basal cell carcinoma; spironolactone, chloramphenicol, and clindamycin for acne and rosacea; platinum nanozymes and nitric oxide donors for alopecia; and CpG-functionalized nanoparticles and photodynamic agents for melanoma and cutaneous malignancies. Conclusion: Nanocarrier technologies exemplify the intersection of colloid chemistry, polymer science, and clinical dermatology. Although formulation stability, batch reproducibility, and translational scalability remain ongoing challenges, emerging innovations, including smart, AI-guided, and hybrid-responsive platforms, offer promising avenues for precision therapy. Significance Statement: By integrating recent advances in nanochemistry with dermatologic pharmacotherapy, this review provides a comprehensive framework for developing next-generation transdermal delivery systems tailored to specific skin diseases. The interdisciplinary progress highlighted here underscores the translational potential of nanocarriers in reshaping dermatologic care.