目的 通过Box-Behnken效应面法优化胆固醇基普鲁兰多糖多柔比星自组装纳米粒(self-assembled doxorubicin-loaded cholesterol-modified pullulan nanoparticle,DOX-CHSP-SAN)的制备工艺。方法 以多柔比星(doxorubicin,DOX)为模型药物,胆固醇基-普鲁兰多糖(cholesterol-modified pullulan,CHSP)为两亲性载体材料,采用透析法制备了DOX-CHSP-SAN,应用Box-Behnken效应面法对其制备工艺进行优化,并对最优处方所制备的DOX-CHSP-SAN形态、粒径、Zeta电位、包封率、载药量及体外释药等进行表征。结果 经优化制得的DOX-CHSP-SAN在电镜下呈圆整球形,平均粒径为(117.1±3.4) nm,polymer dispersity index(PDI)为(0.205±0.023),Zeta电位为(-26.1±0.135) mV,包封率(encapsulation efficiency,EE)为(68.17±0.93)%,载药量(drug loading,DL)为(6.84±0.47)%,其体外释药行为符合Weibull释放动力学模型。 结论 经响应面法优化后制备的DOX-CHSP-SAN形态圆整光滑,粒径小而均匀,包封率和载药量较高,体外释放具有缓释特征。
Abstract
OBJECTIVE To optimize the preparation of self-assembled doxorubicin-loaded cholesterol-modified pullulan nanoparticles(DOX-CHSP-SAN) by response surface methodology. METHODS DOX-CHSP-SAN was prepared by dialysis method with the amphiphilic carrier of cholesterol-modified pullulan (CHSP) and the model drug of doxorubicin(DOX). Box-Behnken Design (BBD) response surface method was used to optimize the preparation process of DOX-CHSP-SAN. The morphology, average particle size, Zeta potentia, the encapsulation efficiency, drug loading of doxorubicin and the drug release characteristics in vitro were determined. RESULTS The optimized DOX-CHSP-SAN has a round spherical shape with an average particle size of (117.1±3.4) nm, PDI of (0.205±0.023), Zeta potential of (-26.1±0.135) mV, the encapsulation efficiency was (68.17±0.93)%, and the drug loading was (6.84±0.47)%. The in vitro release behavior in PBS of pH 7.4 was consistent with the Weibull equation. CONCLUSION The DOX-CHSP-SAN prepared by the dialysis method and optimized by the response surface method is round and smooth, the particle size is small and uniform, the encapsulation efficiency and the drug loading amount are high, and the in vitro release has the sustained release characteristics.
关键词
多柔比星 /
普鲁兰纳米粒 /
Box-Behnken响应面法 /
单因素考察
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Key words
doxorubicin /
pullulan nanoparticle /
Box-Behnken response surface /
single factor study
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参考文献
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脚注
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基金
浙江省教育厅一般科研项目资助(Y201431480);浙江省中医药优秀青年人才基金项目资助(2018ZQ013);浙江省自然科学青年基金项目资助(LQ19H280004);浙江省新苗人才计划项目资助(2018R410052);浙江中医药大学2018年度校级科研基金资助(2018ZJ09)
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