芍药苷固体脂质纳米粒凝胶剂的制备与体外透皮研究

Preparation and in vitro transdermal study of paeoniflorin solid lipid nanoparticle gel

[目的]制备芍药苷固体脂质纳米粒凝胶剂,并评价其体外透皮性能。[方法]采用热熔乳化-均质法制备芍药苷固体脂质纳米粒,以脂药比(X1)、固体脂质浓度(X2)、表面活性剂浓度(X3)作为自变量,以粒径大小(Y1)和包封率(Y2)作为因变量,利用Box-Behnken实验设计优化得到芍药苷固体脂质纳米粒处方,通过透射电镜观察芍药苷固体脂质纳米粒的微观结构;并以卡波姆940作为凝胶基质制备成芍药苷固体脂质纳米粒凝胶剂。采用Franz扩散池法比较了冲和凝胶和芍药苷固体脂质纳米粒凝胶剂的体外透皮吸收性能。[结果]芍药苷固体脂质纳米粒的最佳处方组成为脂药比为80∶1,固体脂质浓度为12.0 mg/mL,表面活性剂浓度为10.0 mg/mL,在透射电镜下可观察到芍药苷固体脂质纳米粒表面光滑圆整,平均粒径为(179.3±10.9)nm,包封率为(91.1±0.9)%。芍药苷固体脂质纳米粒凝胶在12 h内药物单位面积累积透皮量明显高于冲和凝胶,其在皮肤内药物滞留量是冲和凝胶的4.8倍。[结论]将芍药苷制备成固体脂质纳米粒凝胶可以显著提高药物累积透皮量及在皮肤中的滞留量,有望增强芍药苷对皮肤疾病的治疗效果。

[Objective]To prepare paeoniflorin solid lipid nanoparticle gel and evaluate its transdermal performance in vitro.[Methods]The paeoniflorin solid lipid nanoparticle were prepared by hot melt emulsification-homogenization method.The lipid-drug ratio(X1),solid lipid concentration(X2)and surfactant concentration(X3)were used as independent variables,with the average particle size(Y1)and the encapsulation efficiency(Y2)as dependent variables,the optimal formulation of paeoniflorin solid lipid nanoparticle was obtained by Box-Behnken experiment design.The microstructure of paeoniflorin solid lipid nanoparticle was observed by transmission electron microscope.The Carbomer 940 was used as a gel matrix to prepare paeoniflorin solid lipid nanoparticle gel.The in vitro transdermal absorption properties of Chonghe gel and paeoniflorin solid lipid nanoparticle gel were investigated by Franz diffusion cell method.[Results]The optimal formulation composition of paeoniflorin solid lipid nanoparticle as followed:the lipid-drug ratio was 80∶1,the solid lipid concentration was 12.0 mg/mL,and the surfactant concentration was 10.0 mg/mL.The paeoniflorin solid lipid nanoparticle appeared to be spherical with uniform particle size distribution under the transmission electron microscope,the average particle size was(179.3±10.9)nm,and the encapsulation efficiency was(91.1±0.9)%.The drug accumulation transdermal amount of paeoniflorin solid lipid nanoparticle gels was significantly higher than that of Chonghe gel within 12 h,and the drug retention in skin was 4.8 times that of Chonghe gels.[Conclusion]The paeoniflorin solid lipid nanoparticle gel can significantly increase the cumulative transdermal delivery and increase the retention of drugs in the skin,and is expected to enhance the therapeutic effect of paeoniflorin on skin diseases.