ABSTRACT
Objective: To compare the effects of softeners including ethanol, propylene glycol and mixed alcohol (ethanol-propylene glycol 2:8) on the preparation of glabridin ethosomes (GLA-ES), and provide the selection basis of the softeners for studying the ethosomes of insoluble drugs. Methods: GLA-ES were prepared by injection-ultrasonic binding method with ethanol, propylene glycol and mixed alcohol (ethanol-propylene glycol, 2:8) as softeners. The morphology, size, Zeta potential, entrapment efficiency, stability, and in vitro drug release of GLA-ES were investigated. Tyrosinase activity on melanoma B16-OVA cells were detected to evaluate the inhibition of GLA-ES on the synthesis of melanin, the experiment of potassium ferricyanide reducing power was performed to evaluate the antioxidant effect of GLA-ES, and human epidermal HaCaT cells and rat skin were used for preliminary safety evaluation. Results: GLA-ES were yellow translucent liquid, containing vesicular phospholipid bilayer structure, the average particle size of GLA-Et-ES, GLA-PG-ES and GLA-MA-ES were (34.24 ± 0.29), (62.31 ± 1.66) and (41.20 ± 1.13) nm, respectively; The Zeta potential were (-41.0 ± 1.8), (-32.9 ± 0.2) and (-35.8 ± 1.6) mV, the entrapment efficiency were (91.47 ± 2.39)%, (87.33 ± 1.31)% and (91.39 ± 3.59)%, respectively, which had good stability of storage at 4 ℃ for 20 d, in vitro drug release behaviors of GLA-ES fitted Higuchi equation, implying their sustained release properties. Compared with the glabridin suspension, the inhibitory effects of GLA-Et-ES, GLA-PG-ES and GLA-MA-ES on tyrosinase activity in melanoma B16-OVA cells were increased by 38.07%, 19.58% and 40.42%, respectively. The results of potassium ferricyanide reducing power also showed that GLA-ES had a stronger in vitro antioxidant effect than the glabridin suspension; GLA-ES were nearly nontoxic on normal cells and had no irritation to rat skin. Conclusion: GLA-ES can be obtained by hree kinds of softeners, which can inhibit the synthesis of melanin and enhance the antioxidant effect with good safety. The present research will provide the basis for further developing skin-whitening cosmetics or pharmaceutical external preparation. For the insoluble drugs such as glabridin, when mixed alcohol (ethanol-propylene glycol) was selected as the softener to prepare ethosome, it exhibited better encapsulation efficiency and stability than that of ethanol or propylene glycol as the softener alone.