Hair regrowth boosting via minoxidil cubosomes: Formulation development, in vivo hair regrowth evaluation, histopathological examination and confocal laser microscopy imaging.

Minoxidil has been used as an effective and cost-efficient topical treatment for androgenic alopecia. However, due to its poor water solubility, commercially available formulations contain alcohol and propylene glycol in a concentration that causes skin reactions such as irritation and dryness. Therefore, nanotechnology-based formulations can offer an alternative that might increase penetration and deposition of the drug in the skin while minimizing its adverse reactions. Minoxidil cubosomes (MXD-CUB) were prepared by melt dispersion emulsification technique according to full 23 factorial design. Three independent variables, namely, the dispersed phase concentration, glyceryl monooleate: Poloxamer 407 ratio and Tween 80 concentration were tested. Particle size, polydispersity index and the zeta potential were the dependent variables. The optimized formula was investigated by transmission electron microscopy, X-ray diffractometry and in vitro release test. In vivo study included Draize test, histopathological examination, hair regrowth efficacy and confocal laser scanning microscopy (CLSM). Particle size, zeta potential and polydispersity index of the optimal MXD-CUB were measured to be 131.10 ± 1.41 nm, -23.5 ± 0.42 mV and 0.185 ± 0.0, respectively, and its entrapment efficiency was 80.4 ± 4.04 %. Draize test and histopathological testing proved safety and tolerability of MXD-CUB. In vivo hair regrowth study revealed greater hair growth boosting effect of the prepared cubosomes compared to minoxidil solution. CLSM proved superior penetration and retention of rhodamine B-loaded cubosomes in the skin compared to rhodamine B solution. Therefore, MXD-CUB can be a safe and effective dosage form for minoxidil that overcome the drawbacks of the commercial formulations.