Vesicular Drug Delivery Systems With Skin Permeation Enhancers: A Review of Formulation and Evaluation for Topical and Transdermal Applications

Skin permeation remains a major challenge in the effective delivery of drugs through topical and transdermal routes due to the barrier function of the stratum corneum. Vesicular drug delivery systems, such as liposomes, niosomes, transfersomes, and ethosomes, have emerged as promising carriers to enhance drug penetration and improve therapeutic efficacy. This review focuses on the role of skin permeation enhancers incorporated within vesicular systems to overcome the limitations of conventional topical formulations. Permeation enhancers act by disrupting the lipid structure of the stratum corneum, altering protein conformation, or increasing drug partitioning into the skin, thereby facilitating improved drug diffusion. Various classes of permeation enhancers, including chemical agents (such as alcohols, fatty acids, surfactants, and terpenes) and novel biological enhancers, are discussed in relation to their mechanisms and compatibility with vesicular carriers. The synergistic effect of combining vesicular systems with permeation enhancers significantly improves drug bioavailability, targeting efficiency, and controlled release profiles. Additionally, the review highlights recent advancements in deformable vesicles and nanovesicular systems designed for enhanced transdermal delivery. Despite their advantages, issues such as skin irritation, toxicity, and stability remain challenges that need careful consideration. Overall, vesicular drug delivery systems integrated with effective permeation enhancers represent a promising approach for non-invasive drug administration. Future research should focus on optimizing formulations to achieve maximum efficacy with minimal adverse effects, paving the way for improved topical and transdermal therapeutic strategies.