Transdermal Liposomal Delivery Systems: Advantages, Applications, Challenges, and Prospects

Transdermal drug delivery systems (TDDS) offer a noninvasive route for delivering active compounds directly to lesion sites while bypassing hepatic first-pass metabolism, thereby reducing systemic side effects and improving patient compliance. As such, TDDS have gained significant attention in disease treatment. However, the stratum corneum presents a major barrier to drug permeation due to its “brick-and-mortar” structure, limiting the effectiveness of transdermal strategies. Developing safe and efficient enhancement methods remains a major challenge. Among various drug delivery platforms, liposomal systems have attracted increasing interest owing to their nanoscale size, biocompatibility, high drug-loading capacity, and ability to protect drugs from enzymatic degradation. These carriers also interact favorably with skin lipids, enhancing drug penetration. Advances in nanotechnology have led to the development of novel liposomal formulations such as ethosomes, transfersomes, niosomes, and pharmacosomes, each tailored to address specific therapeutic needs. This review summarizes recent progress in liposome-based TDDS for both skin and systemic diseases, highlighting their mechanisms of action, therapeutic benefits, and clinical translation potential. Additionally, it explores future directions and ongoing challenges, aiming to provide a reference for advancing liposomal technologies in transdermal drug delivery.