Enhanced ex vivo skin retention of bicalutamide using a nano-in-micro composite: Drug-loaded lipid vesicles in a dissolving microarray patch

Antiandrogens are a family of drugs that block the biological effects of androgens, which are commonly used to treat a plethora of androgen-dependent conditions. However, their effectiveness highly depends on treatment compliance and their use is not exempt from side effects. Bicalutamide (BIC) is a testosterone blocker that, due to its peripheral tissue selectivity, offers the advantage of fewer side effects compared to other antiandrogens such as finasteride or dutasteride. In this study, BIC-loaded lipid vesicles (LVs) were developed and incorporated into a PVP/PVA-based Dissolving Microarray Patches (BIC-LVs@DMAPs) for BIC skin local delivery. First, the mechanical and insertion properties of the BIC-LVs@DMAPs were assessed. Then, the in vitro biocompatibility of the formulation was determined in keratinocytes. Finally, the effectiveness of the formulation to deliver BIC through skin was explored ex vivo using murine skin. BIC-LVs@DMAPs exhibited optimal mechanical and insertion properties to effectively perforate the stratum corneum and facilitate the passage of BIC-LVs. Ex vivo studies demonstrated the efficacy of BIC-LVs@DMAPs to improve the skin retention of BIC, while in vitro cytotoxicity results ensured their safety profile. Overall, these results pave the way for further in vivo studies and clinical application to improve the current early stages androgenetic alopecia topical treatments.