Black phosphorus nanosheets encapsulated microneedle for multifunctional therapy for androgenic alopecia

BACKGROUND: Androgenetic alopecia (AGA), a chronic and progressive disease, significantly impacts the patients' social, emotional, and mental well-being. Current treatment for AGA are mainly limited by drug side effects and the stratum corneum (SC) barrier of scalp. RESULTS: To address these issues, we developed a microneedle (MN) system loaded with black phosphorus nanosheets (BP) encapsulating baicalin (BA), a natural ingredient, for effective treatment of AGA. We first fabricated BP-BA based on the BP properties of high drug loading capacity and excellent photothermal conversion efficiency. Upon 635 nm laser irradiation, BP-BA demonstrated efficient photothermal conversion to mild thermal of ~ 42 °C. This mild thermal effect controlled BA's stimuli-responsive release, enhanced cellular uptake, and effectively modulated gene expression in dihydrotestosterone-treated human dermal papilla cells, downregulating negative regulators such as SRD5A2, AR, DKK1, and TGFB1, while upregulating positive regulators like CTNNBIP1 and VEGFA. Furthermore, we encapsulated BP-BA to MN fabricating BP-BA@MNs to overcome the SC barrier. Compared with BP-BA@MNs without laser irradiation, BP-BA@MNs with laser irradiation significantly enhanced drug penetration into the subcutaneous area and accumulation at the follicular site. Importantly, BP-BA@MNs demonstrated synergistic efficacy against testosterone-induced AGA in vivo through combining BA chemotherapy, BP-mediated mild photothermal therapy, and MN delivery, as well as good biocompatibility and biosafety, and the underlying synergistic mechanism was elucidated in terms of follicular microenvironment reconstruction. CONCLUSIONS: This combining BP mild photothermal and MN system is a promising approach for follicular targeted drug delivery, providing a multifunctional strategy for addressing the clinical needs of anti-AGA.