Box-Behnken设计-效应面法优化岩黄连碱纳米结构脂质载体处方工艺及体外药效评价  

Formulation optimization of dehydrocavidine nanostructured lipid carriers by Box-Behnken design response surface method and pharmacodynamic studies in vitro

作　　者：苏晓丹 麦琬婷 钟华帅 曾勇珠 陆建媚 覃裕翠 黄秋洁 叶勇[1,3] SU Xiao-dan;MAI Wan-ting;ZHONG Hua-shuai;ZENG Yong-zhu;LU Jian-mei;QIN Yu-cui;HUANG Qiu-jie;YE Yong(School of Pharmacy,Guangxi Medical University,Nanning 530021,China;School of Pharmacy,Guangxi University of Traditional Chinese Medicine,Nanning 530001,China;Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation,Nanning 530021,China)

机构地区：[1]广西医科大学药学院,广西南宁530021 [2]广西中医药大学药学院,广西南宁530001 [3]广西生物活性分子研究与评价重点实验室,广西南宁530021

出　　处：《中草药》2022年第22期7019-7028,共10页Chinese Traditional and Herbal Drugs

基　　金：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(2022GXNSFDA 035063);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)。

摘　　要：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10.0 mg、固-液脂质比为1∶8、卵磷脂用量为85.0 mg、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.

关 键 词：岩黄连碱 纳米结构脂质载体 Box-Behnken设计-效应面法 缓释 MTT法 药效评价 溶剂蒸发法 肝纤维化 

分 类 号：R283.6[医药卫生—中药学]