Octaarginine nanocomplex encapsulated with hyaluronic acid-modified CuS for enhanced transdermal delivery of insulin

Transdermal delivery is considered as a promising convenient and painless approach for the delivery of insulin. In this study, an amphiphilic peptide derivative of oleic acid modified octaarginine (R8-OA) and a photothermal nanomaterial of hyaluronic acid modified CuS (CuS-HA) were successfully synthesized. Using both materials as carriers, CuS-HA enveloped R8-OA@insulin nanocomplexes (HERNCs) were prepared. In vitro studies demonstrated that R8-OA could chemically enhance the penetration of insulin through the stratum corneum. In vivo laser activation studies suggested that CuS-HA in HERNCs could ablate the stratum corneum, thus facilitating the insulin penetration through physical enhancement. The hypoglycemic effect study revealed that blood glucose level in diabetic mice decreased to 42.3% within 4 h, and the value was maintained at 75.1% after 24 h. These results underscored the potential of the enveloped nanocomplexes for enhanced transdermal delivery of insulin.