Self-Assembled Skin-Penetrating Peptides with Controlled Supramolecular Properties for Enhanced Transdermal Delivery
Jeon Hyeong Kang, Jieun Kim, Jae Yun Lee, Donghyun Kang, Hyun Jin Kim, Kyobum Kim, Woo‐jin Jeong
Abstract
The use of nanocarriers decorated with penetration-enhancing agents (PEAs) is considered to be a promising approach for efficient transdermal delivery. In this study, we developed short amphiphilic skin-penetrating peptides (17 amino acids) that functioned not only as PEAs but also as building blocks of nanocarriers without the incorporation of additional macromolecules for self-assembly and guest molecule encapsulation. Interestingly, varying only two amino acids in the hydrophobic moiety of the peptides resulted in significantly different self-assembly behavior, thermal stability, protease resistance, and skin-penetration efficiency in a human skin model. The analysis of the peptide secondary structure revealed that such characteristic changes arose due to the sequence variation-mediated conformational change in the hydrophobic block. These findings hold significant promise for the development of simple and effective delivery systems exhibiting controllable supramolecular properties.