Abstract

The transdermal route has drawn considerable attention and has emerged as a solid alternative to mimic the drawbacks of drugdelivery through the oral and parenteral routes. However, the effectiveness of TDDS is often limited by the skin's outermost layer, the stratumcorneum (SC), which acts as a barrier to drug diffusion. In addition, the drug molecule's molecular weight, hydrophilicity, and ionic nature canalso impact its transdermal delivery. Various methods have been developed to overcome these limitations to facilitate drug penetration acrossthe SC, including nano-carriers, wearable delivery systems, and combination-based approaches. The use of nano-carriers, such as dendrimers,liposomes, niosomes, and micro sponges, has shown promise in enhancing the efficacy of TDDS. Another emerging innovation for TDDS iswearable delivery systems, which offer non-invasive, convenient, and extended drug administration. Additionally, combination-based approaches,such as ultrasound and microneedle-based systems or ultrasound and electrical-based techniques, are also being investigated and are the centerof attraction in the research of TDDS approaches. This review summarizes a combination of all different novel penetration enhancementtechniques used to enhance the efficacy of transdermal drug delivery systems that were not precisely captured by other review articles. Most ofthe review articles emphasized these penetration enhancement techniques separately. However, a careful review of all the penetrationenhancement techniques in one article is missing. Thus, the purpose of this article is to comprehensively review and summarize the recentlyused penetration enhancement techniques along with the possible mechanism of action in a single article. Our primary aim is to collect relevantreviews and research articles by searching various databases to provide a comprehensive overview of the field. By providing a comprehensiveoverview of the available techniques, this review article will help students and researchers stay up-to-date with the latest developments in thefield of novel penetration enhancement techniques used to increase the efficiency of TDDS.

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