Stability of polylactic acid particles and release of fluorochromes upon topical application on human skin explants

Particle-based drug delivery systems allow the controlled and targeted release of incorporated active compounds to the skin and are promising tools to improve the efficacy of topical therapies. In this study we investigated the stability and release properties of biodegradable polylactic acid (PLA) particles upon topical application on human skin explants. PLA particles loaded with the hydrophilic fluorochrome 4-Di-2-Asp (DiAsp-PLA) were compared to PLA particles loaded with the lipophilic fluorochrome Bodipy 630/650 (BP-PLA). Changes of the particle morphology after their incubation on skin surface were investigated by means of electron microscopy while fluorescence microscopy and flow cytometry were used to evaluate particle penetration in hair follicles and fluorochrome release. We found that BP-PLA particles released rapidly the loaded fluorochrome and lost the particulate morphology within a few hours after application on skin surface. On the contrary, DiAsp-PLA particles maintained the particulate morphology, accumulated in hair follicles, and allowed a constant release of the incorporated fluorochrome for up to 16 h. These results show that, once applied to skin surface, PLA particles release the incorporated fluorochromes in a time-dependent manner and suggest the perspective to modulate particle stability and release properties by incorporating excipients with different degree of lipophilicity.