目的 运用Box-Behnken设计-效应面法优化姜黄素-乳铁蛋白纳米粒(curcumin-lactoferrin nanoparticles,Cur-LF-NPs)的制备处方工艺。方法 采用去溶剂化法制备Cur-LF-NPs,基于单因素实验结果,选择反溶剂/溶剂体积比、乳铁蛋白/姜黄素投料比和pH值作为后续Box-Behnken设计优化实验的考察因素;以包封率、粒径和多分散系数经CRITIC权重分析计算后得到的综合评分作为评价指标,使用Design Expert 10软件对数据进行拟合并验证优化后的处方工艺。最后对纳米粒形态、粒径电位、载药能力、稳定性及体外释放行为等进行表征评价。结果 经优化后的制备工艺条件为反溶剂/溶剂体积比16:1、乳铁蛋白/姜黄素投料比8:1、pH值为6。Cur-LF-NPs粒径为(72.6±5.2)nm、PDI为0.084±0.015、ζ电位为(24.5±3.7)mV,包封率(94.8±1.6)%、载药量(10.2±0.5)%。Cur-LF-NPs体外释放相较于姜黄素原料药具有一定的缓释效果。结论 经Box-Behnken设计-效应面法筛选获得制备Cur-LF-NPs的最佳处方工艺,该制剂粒径均一、载药能力强、稳定性好,为后续的体内外研究提供稳定的制剂基础。

Objective To optimize prescription process of curcumin lactoferrin nanoparticles (Cur-LF-NPs) by Box-Behnken design-response surface method.Methods Cur-LF-NPs were prepared by the desolvation method.Based on the results of single factor experiment,the anti-solvent/solvent volume ratio,lactoferrin/curcumin weight ratio and pH value were selected as the investigational factors for the subsequent Box-Behnken design optimization experiment.The comprehensive score of entrapment efficiency,particle size and polydispersity coefficient obtained by CRITIC weight analysis and calculation were chosen as the evaluation parameters,and simulated and verified by Design Expert 10 software.Finally,the physical property of Cur-LF-NPs,including the morphology,particle size,potential,drug loading capacity,stability andin vitro release behavior were characterized and evaluated.Results The optimized prescription process were obtained as follows:the volume ratio of anti-solvent/solvent was 16:1,the weight ratio of lactoferrin/curcumin was 8:1 and the pH value was 6.The particle size of Cur-LF NPs was (72.6 ±5.2) nm,the PDI was 0.084 ±0.015,and the ζ potential was (24.5 ±3.7) mV;The entrapment efficiency was (94.8 ±1.6)%,and the drug loading was (10.2 ±0.5)%.Compared with free curcumin,theinvitro release of Cur-LF-NPs has a certain sustained-release effect.Conclusion The process for the preparation of Cur-LF-NPs was optimized by the Box-Behnken design-response surface screening method,the Cur-LF-NPs showed uniform particle size,good drug loading capacity and acceptable stability.This study provided a solid preparation basis for futurein vitro and in vivo research of Cur-LF-NPs.

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国家自然科学基金面上项目(82073994);四川省科技计划重点研发项目(2020YFN0152);四川省科技厅科技项目(2020JDJQ0049);农业部杂粮加工重点实验室开放课题(2019CC02);成都中医药大学杏林学者学科人才科研提升计划(QJJJ2021002)