Enhanced transdermal delivery of curcumin nanosuspensions: A mechanistic study based on co-localization of particle and drug signals

Abstract

Nanosuspensions have received much attention in enhanced transdermal delivery. However, the corresponding mechanisms have not been clarified. In particular, whether nanosuspensions can directly penetrate across the stratum corneum (SC) and what is the transdermal route for the enhanced penetration. Therefore, curcumin (CUR) was adopted in this study as a model drug, while an aggregation-caused quenching (ACQ) probe was physically embedded in CUR nanosuspensions, i.e., the CUR hybrid nanosuspensions (CUR-HNSs), for bioimaging. The ACQ properties enable identification of intact CUR-HNSs. The co-localization of particle and CUR signals was exploited to outline the translocation profiles of intact nanosuspensions as well as the cargoes. Three sizes of CUR-HNSs are prepared, which are spherical and amorphous. CUR is poor in transdermal transport even in propylene glycol solution, which was enhanced by nanosuspensions. Although 400 nm CUR-HNSs present higher steady state flux than 140 nm and 730 nm ones, the cumulative amount of permeated CUR is yet less than 2% of the applied dose at 12 h. Co-localization of CUR and ACQ probe signals indicates that CUR-HNSs can infiltrate into the SC layer and accumulate in the hair follicles. The intact CUR-HNSs cannot enter into the skin. On the contrary, CUR molecules diffuse into the whole skin tissues following dissolution of CUR-HNSs in the SC and the hair follicles. In conclusion, nanosuspensions are advantageous for transdermal delivery of poorly permeable drugs by filtrate into the SC and accumulate in hair follicles.

Keywords: Aggregation-caused quenching; Co-localization; Curcumin; Hair follicle; Nanosuspensions; Transdermal delivery.