Liposomes enhance the hair follicle delivery of minoxidil sulfate with improved treatment of androgenic alopecia.

Androgenic alopecia (AGA) represents one of the most prevalent forms of hair loss. Liposomes (LPSs), acting as a localized dermal drug reservoir with sustained release property, can effectively prolong and enhance drug retention within the skin. Minoxidil sulfate (MXS), a potent active metabolite of minoxidil (MX) for promoting hair growth, exhibits instability in aqueous solution and faces difficulties in depositing within the deep dermal hair follicle regions. In this study, MXS-LPSs were fabricated via the thin-film hydration-dispersion method combined with an ammonium sulfate gradient active drug loading process, and their physicochemical characteristics were comprehensively characterized. The skin permeation/deposition properties of the drug from the MXS-LPSs were investigated by Franz diffusion cell method on ex vivo rat skin, and the mechanism underlying the targeted drug delivery of LPSs to hair follicles was explored by confocal laser scanning microscopy (CLSM). The pharmacodynamic evaluation of MXS-LPSs was carried out in AGA model rats. The optimized MXS-LPSs were uniformly dispersed with enhanced stability. The average vesicle size of MXS-LPSs was 129.46 ± 7.04 nm, the zeta potential was -25.57 ± 4.79 mV, the encapsulation efficiency (EE) was 92.72 ± 0.75 %, and the drug loading (DL) was 2.80 ± 0.12 %. The results of ex vivo skin permeation/deposition showed that the cumulative permeated drug amount (Qn) from MXS-LPS, MX tincture and MXS solution at 36 h was 225.98 ± 11.53, 19.79 ± 1.97 and 584.42 ± 2.33 μg·cm-2, respectively. The deposited drug amount in the skin beneath the stratum corneum from MXS-LPSs, MX tincture and MXS solution accounted for about 59.80 ± 26.27 %, 43.18 ± 6.58 % and 32.55 ± 1.61 % of that in the whole skin, respectively. It is remarkable that MXS-LPSs showed a considerably increased accumulation in hair follicles when compared to MXS solution. The results of pharmacodynamic tests demonstrated that, compared to MX tincture, MXS-LPSs could more effectively stimulate hair regrowth and avoided the adverse effects. Importantly, the MXS-LPSs also reduced skin irritation and sensitization. Consequently, MXS-LPSs hold substantial promise in the treatment of AGA.