白及多糖脂质体的制备及其体外透皮吸收考察

Preparation of Bletilla Striata Polysaccharide Liposome and Its Transdermal Absorption In Vitro

目的采用星点设计-响应面法筛选并优化白及多糖脂质体的处方及制备工艺,并对其进行质量评价,以及考察其体外透皮吸收效果。方法采用逆向蒸发法制备白及多糖脂质体,通过星点设计-响应面法优化制备工艺和处方,测定最优处方下的白及多糖脂质体粒径、多分散系数(PDI)及Zeta电位;透析法研究其体外释放情况,采用透皮扩散仪对其体外经皮扩散情况进行测定并对释放曲线进行拟合。结果优化后的脂质体制备处方:磷脂浓度、胆固醇与磷脂比、磷脂与药物比分别为1.44%、1∶2.13、1∶42;最终工艺:乳化时间10 min、水化时间40 min、粒径破碎时间10 min。最优处方下的脂质体Zeta电位为-(18±1.3)mV,平均粒径为(172.2±5.20)nm,PDI为(0.241±0.0104),载药量为(0.93±0.013)%,平均包封率为(69.65±9.7)%,药物质量浓度为(334±7.3)μg·mL^(-1)。白及多糖脂质体在第12小时的累积释放率为52.2%,拟合方程符合Higuchi方程;累积透皮率18.06%,拟合方程符合Higuchi方程;第12小时皮肤滞留量为33.8μg·g^(-1)。结论所制备的白及多糖脂质体粒径均匀,经过筛选后包封率增加,对比于白及多糖,其脂质体有明显缓释效果,皮肤滞留量更大,可作为长效透皮制剂。

Objective The formulation and preparation technology of Bletilla striata polysaccharide liposomes were screened and optimized by central composite design-response surface optimization methodology.Next,its quality was evaluated,and its transdermal absorption effect in vitro was investigated.Methods Bletilla striata polysaccharide liposomes were prepared by reverse evaporation method.The preparation technology and prescription were optimized by using central composite design-response surface methodology.The particle size,polydispersion index(PDI)and Zeta potential of optimized polysaccharide liposomes were determined.Dialysis method was used to study the release of Bletilla striata polysaccharide liposomes in vitro.The transdermal diffusion of Bletilla striata polysaccharide liposomes in vitro was measured by transdermal diffuser and the release curve was fitted.Results The optimized liposome prescription was as follows:phospholipid concentration,ratio of cholesterol to phospholipid,ratio of phospholipid to drug are 1.44%,1∶2.13 and 1∶42,respectively.The final process are emulsification time being 10 minutes,hydration time being 40 minutes,crushing time being 10 minutes.Zeta potential of the liposome under the optimal prescription is-(18±1.3)mV,the average particle size is(172.2±5.20)nm,the PDI is(0.241±0.0104),the drug loading is(0.93±0.013)%,the average encapsulation efficiency is(69.65±9.7)%,and the drug concentration is(334±7.3)μg·mL^(-1).The cumulative release rate of Bletilla striata polysaccharide liposomes at the twelfth hour is 52.2%.The fitting equation met the Higuchi equation,and the cumulative skin penetration rate is 18.06%,the fitting equation also met the Higuchi equation,and the skin retention at the twelfth hour is 33.8μg·g^(-1).Conclusion The prepared liposomes of Bletilla striata polysaccharide have uniform particle size and show high entrapment efficiency after optimization.Compared with Bletilla striata polysaccharide,the final liposomes have obvious slow-release effect and high skin retention,and can be used as a long-acting transdermal preparation.