Mechanistic Analysis of Human Skin Distribution and Follicular Targeting of Adapalene-Loaded Biodegradable Nanospheres With Insight Into Hydrogel Matrix Influence, In Vitro Skin Irritation, and In Vivo Tolerability

In 2017, researchers developed a biocompatible nanomedicine for the follicular delivery of adapalene (AD), aimed at treating acne vulgaris with reduced irritation potential. Adapalene was successfully loaded into poly-ε-caprolactone nanospheres (NS) with high encapsulation efficiency (84.73% ± 1.52%), appropriate particle size (107.5 ± 8.19 nm), and negative zeta potential (−13.1 mV), which allowed for sustained release. These nanospheres were incorporated into hydroxypropyl methylcellulose (HPMC) or hyaluronate (HA) gels, and their skin distribution was analyzed. The nanoparticle dispersion led to higher AD retention in skin layers compared to AD suspension, with NS-HPMC reducing and NS-HA increasing AD retention across all skin layers. Confocal laser scanning microscopy (CLSM) showed that the NS were localized in hair follicles, with HPMC gel limiting NS to the upper skin layers and HA gel promoting deeper penetration. The formulation with HA gel–dispersed AD-NS was found to be non-irritating through in vitro and in vivo studies, making it a suitable treatment option for oily, acne-prone skin.