Minoxidil cyclodextrin inclusion complex-loaded microemulsions and transfersomes for androgen alopecia treatment: a...

Our MXD/SCD@TF designed by the combination of transfersome and inclusion technology was obviously superior to commercial 2% MXD tincture in treating androgenetic alopecia (AGA) in mice, but its complex preparation and poor stability undoubtedly increased both development and usage costs. In this paper, using our previous alcohol-free low surfactant microemulsion technology with VES as auxiliary oil phase, microemulsions loaded with the inclusion complex of MXD and sulfobutylether-β-cyclodextrin (SBE-β-CD) were prepared, optimized and characterized, and the therapeutic effect on AGA C57BL/6 mice was compared with MXD/SCD@TF. According to the ternary phase diagram, steady-state permeation rate of MXD through SD rat skin and drug retention, MXD/SCD@ME was selected as the optimal prescription, composed of 5.25% oil phase, 9.75% surfactants, 10.20% SBE-β-CD, 1.02% MXD and 73.78% water, which conformed to the characteristics of microemulsion. MXD/SCD@ME had good stability, and the application of inclusion technology increased the MXD loading in microemulsion to nearly 5 times. The results of in vivo skin penetration test and laser confocal scanning visualization showed that MXD/SCD@ME was easier to deliver drugs to deeper skin tissues than MXD/SCD@TF. Hair regeneration study demonstrated that MXD/SCD@ME had higher ability than MXD/SCD@TF in promoting hair growth, prolonging hair growth period, reducing ROS level and promoting cell proliferation of hair follicles. In addition, the blank microemulsion of MXD/SCD@ME had certain therapeutic effect on AGA, indicating the synergistic effect between VES and MXD. All these indicated that MXD/SCD@ME is expected to provide a better choice for pharmacological therapy of MXD on AGA than MXD/SCD@TF.