Polycaprolactone nanoparticles for targeted and prolonged topical delivery of azithromycin to pilosebaceous follicles

Abstract

Topical administration of antibiotics for localized skin infections offers advantages over systemic therapies, including reduced side effects and minimized antimicrobial resistance. However, when using azithromycin topically to treat acne, the low capacity of this potent antibiotic to reach the affected pilosebaceous units compromises therapy. This study aimed to develop azithromycin-loaded polymeric nanoparticles to enhance follicular targeting and improve topical drug delivery. Thermal analyses showed compatibility and miscibility between azithromycin and polycaprolactone. The polymeric nanoparticles produced by the nanoprecipitation method were spherical, monodisperse (158.3 ± 0.4 nm; PdI<0.1), achieved an entrapment efficiency of 92.5 ± 0.1 % for azithromycin, and exhibited a sustained drug release profile over 12 h. They enhanced drug deposition in pilosebaceous follicles compared to the control drug solution over 24 h. Indeed, 43 ± 6 % of the drug was localized in follicles after 24 h of skin treatment–a fivefold (p < 0.05) increase in the targeting factor relative to control. The nanodispersion was also demonstrated to be non-irritant. In conclusion, the polycaprolactone nanoparticles effectively targeted and prolonged azithromycin delivery to hair follicles while minimizing systemic exposure, offering a promising strategy for the topical treatment of follicle-associated infections.