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摘要
Objective: To prepare the glabridin/hydroxypropyl-β-cyclodextrin (GLA/HP-β-CD) inclusion complex-loaded dissolvable microneedles and characterize the physicochemical profile and transdermal drug release in vitro and in vivo. Methods: The GLA/HP-β-CD inclusion complex was prepared by solution stirring-freeze drying method. The inclusion constant and inclusion ratio were determined by phase solubility method. The inclusion complex was characterized by Fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), differential scanning calorimetry (DSC) and X-ray diffraction (X-RD). The effect of cyclodextrin inclusion on the biological activity of GLA was investigated. The dissolvable microneedles loaded with inclusion complex was prepared, the appearance and in vitro release of which were investigated. The in vitro transdermal delivery of GLA from the microneedles was further studied using modified Franz diffusion cell. Finally, preliminary investigation of the intradermal delivery of the drug after microneedle administration was carried out in mice. Results: The formation of inclusion was proved by multiple characteristic results. The entrapment efficiency of the optimized formulation was 57.85%, with a drug loading of 13.28%. The inclusion with cyclodextrin had little effect on the antioxidant activity and tyrosinase inhibitory activity of GLA in vitro. The in vitro release test showed that the GLA/HP-β-CD microneedles had a significant sustained release effect (P< 0.01) compared with GLA microneedles. In vitro transdermal experiments showed that the initial penetration rate, the cumulative amount and skin retention in the GLA/HP-β-CD microneedle group were higher than those in GLA microneedle group and GLA suspension group. Besides, the time lag was shorter (P< 0.05). In vivo experiments showed that the GLA/HP-β-CD microneedles quickly reached a higher skin retention after administration than the GLA microneedles did, and the maintenance time is longer. Conclusion: The cyclodextrin inclusion could greatly improve the solubility of GLA in water. The combination of the inclusion complex and dissolvable microneedles enhanced the transdermal penetration of GLA, thus indicated a sustained release. This novel drug delivery system is expected to improve the whitening and freckle effect of GLA, which has potential application value.
