Tracking the transdermal penetration pathways of optimized curcumin-loaded chitosan nanoparticles via confocal laser scanning microscopy

Curcumin-loaded chitosan nanoparticles intended for transdermal delivery were successfully prepared, optimized and their fate, interaction and pathway through the skin were tracked. D-optimal response surface methodology was used for the nanoparticles optimization. Xy and z-stack confocal laser scanning microscopic images were used for the particles tracking after measuring the drug permeation through the skin using Franz diffusion cells. Very small particle sizes in the range of 33.85-199.23 nm accompanied with low PDI values of 0.129-0.536 of the prepared curcumin-loaded chitosan nanoparticles were obtained. TEM images revealed the spherical and non-aggregating curcumin-loaded chitosan nanoparticles. The ex-vivo permeation studies have proven the ability of the prepared chitosan nanoparticles to deliver curcumin through the skin reaching fluxes viz 5.14 +/- 1.31 mu g cm(-2) h(-1). The confocal laser scanning microscopy has proven that the appendageal route is the main route of penetration of the prepared nanoparticles and has demonstrated the localization of the chitosan nanoparticles within the hair follicles from which the drug diffuses to deep layers of the skin and beyond. (C) 2017 Elsevier B.V. All rights reserved.