目的 Box-Behnken设计-效应面法优化岩黄连碱纳米结构脂质载体(dehydrocavidine nanostructured lipid carriers,DC-NLCs)处方,并进行体外药效研究。方法 采用溶剂蒸发法制备DC-NLCs。以包封率、载药量和ζ电位为考察指标,采用单因素考察和Box-Behnken设计-效应面法优化DC-NLCs的处方。对DC-NLCs进行表征,并考察体外药效作用。结果 最佳处方为投药量为10.0mg、固-液脂质比为1:8、卵磷脂用量为85.0mg、表面活性剂为1%聚山梨酯-80。DC-NLCs测得包封率为(85.29±0.01)%,载药量为(6.27±0.00)%,ζ电位为(-17.90±1.09)mV、粒径为(188.50±11.77)nm,体外释药具有明显的缓释特征。体外药效学实验表明,DC-NLCs体外抑制肝纤维化的效果显著。结论 Box-Behnken设计-效应面法所建立的模型能较好地用于DC-NLCs处方优化,准确度高,预测效果较好,且优化制备的DC-NLCs具有显著的抑制肝纤维化作用。

Objective To optimize the formulation of dehydrocavidine nanostructured lipid carriers (DC-NLCs) by Box-Behnken design response surface method, and study in vitro pharmacodynamics. Methods Preparation of DC-NLCs by solvent evaporation. Encapsulation efficiency, drug loading and potential were used as evaluation index, single factor investigation method and Box-Behnken response surface method (BBD-RSM) were used to investigate the optimal prescriptions of DC-NLCs. The DC-NLCs were characterized and in vitro efficacy results were compared. Results The optimal formulation: dehydrocavidine dosage was 10.0 mg, solid-liquid lipid ratio was 1∶8, lecithin dosage was 85.0 mg, surfactant was 1% polysorbate-80. Envelopment efficiency, drug loading, potential and particle size of DC-NLCs were (85.29 ±0.01)%, (6.27 ±0.00)%, (-17.90 ±1.09) mV and (188.50 ±11.77) nm, respectively. In vitro drug release has obvious sustained-release characteristics. In vitro pharmacodynamic experiments showed that DC-NLCs had significant inhibitory effect on liver fibrosis. Conclusion It is feasible to apply BBD-RSM for the formulation optimization of DC-NLCs, and DC-NLCs had significant inhibitory effect on liver fibrosis.

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国家自然科学基金资助项目（81960756）；国家自然科学基金资助项目（81360689）；广西自然科学基金资助项目（2022GXNSFDA035063）；广西自然科学基金资助项目（2018GXNSFAA050078）；广西自然科学基金资助项目（2015GXNSFAA139173）；广西高校中青年教师科研基础能力提升基金资助项目（2019KY0148）；广西高校中青年教师科研基础能力提升基金资助项目（2019KY0315）