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利用Box-Behnken效应面法优化Fe3O4纳米颗粒的处方及其体外释药机制研究

Optimization of the Formulation of Fe3O4 Nanoparticles by Box-Behnken Response Surface Method and Its Drug Release Mechanism In Vitro
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摘要 目的对自制的聚乙二醇(PEG)修饰的四氧化三铁(Fe3O4)纳米颗粒进行处方优化,并对其体外释药机制进行研究。方法采用Box-Behnken效应面法优化Fe3O4纳米颗粒的处方;通过测定不同时间点Fe3O4纳米颗粒的粒径考察其常温下物理化学稳定性;利用超声搅拌法制备分别负载盐酸多柔比星、灯盏乙素、氟尿嘧啶3种不同类型药物的Fe3O4纳米颗粒,并采用透析法对Fe3O4纳米颗粒的释药能力进行研究,再应用不同的数学模型拟合释药数据,阐释其释药机制;最后在不同温度下考察Fe3O4纳米颗粒的释药能力,说明其光热效应对药物释放的影响。结果常温下Fe3O4纳米颗粒粒径在20~30 nm之间;Fe3O4纳米颗粒负载水溶性药物氟尿嘧啶时与5种模型的拟合度均不高,负载盐酸多柔比星时与Higuchi方程的拟合度较高,而负载灯盏乙素时与零级方程和Hixson-Crowell方程的拟合度均达到0. 996 7,且用于机制验证的Ritger-Peppas方程指出,Fe3O4纳米颗粒装载亲水性药物时释药机制为简单的扩散,而装载疏水性药物时主要通过溶蚀机制进行零级控制释放;随着温度升高,Fe3O4纳米颗粒的释药能力增加。结论疏水性药物可通过超声搅拌的方法载入Fe3O4纳米颗粒中以提高其生物相容性,为难溶性药物的新剂型研究开发奠定了实验基础。 OBJECTIVE To optimize the formulation of Fe3O4 nanoparticles modified with polyethylene glycol (PEG)through Box-Behnken response surface method.To investigate its release properties in vitro to provide references for the study of drug delivery system. METHODS Firstly, the formulationof Fe3O4 nanoparticles was optimized by Box-Behnken response surface method. Secondly, the physical and chemical stabilities of Fe3O4 nanoparticles were determined at different stages. Next, doxorubicin hydrochloride, scutellarin and 5-fluorouracil were respectively loaded into Fe3O4 nanoparticles by ultrasonic stirring method and the drug release ability of Fe3O4 nanoparticles was studied by dialysis method. Finally, different mathematical models were applied to fit the release data to explain the release mechanism, and the release ability of Fe3O4 nanoparticles was investigated at different temperatures to clarify the effect of photothermal effect on drug release. RESULTS The particle size of Fe3O4 nanoparticles was from 20 to 30 nm at room temperature. Fe3O4 nanoparticles loading with water-soluble drugs 5-fluorouracil was incompatible with the five models. However, when doxorubicin hydrochloride was loaded, its release fitted well with the Higuchi equation. And both zero-order equation and the Hixson-Crowell equation can match well with such Fe3O4 nanoparticles loading with scutellarin. Finally, it can be clarified with mechanism-verified Ritger-Peppas equation that the simple diffusion motivated the drug release of Fe3O4 nanoparticles loaded with hydrophilic drugs, and the Zero dissolution release mechanism worked when loaded with hydrophobic drugs.As the temperature increases, the release ability of Fe3O4 nanoparticles was increases. CONCLUSION Hydrophobic drugs can be loaded with SCU in the Fe3O4 nanoparticles by ultrasonic stirring method to improve the biocompatibility of the drugs, which provide some experimental foundation for the research and development of new formulations of poorly soluble drugs.
作者 赵青 陈思颖 吴耽 刘帆 王爱民 刘亭 杨畅 ZHAO Qing;CHEN Si-ying;WU Dan;LIU Fan;WANG Ai-min;LIU Ting;YANG Chang(State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550004, China;Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang 550004, China;School of Pharmacy, Guizhou Medical University, Guiyang 550025, China;Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Medical University, Guiyang 550004, China;National Engineering Technology Research Center of Miao′s Medicine, Guiyang 550004, China)
出处 《中国药学杂志》 CAS CSCD 北大核心 2019年第9期711-719,共9页 Chinese Pharmaceutical Journal
基金 国家自然科学基金项目资助(81860323,81760699) 贵州省科技厅贵州医科大学科学技术联合基金项目资助[黔科合LH字(2016)7364号] 贵州省科学技术厅人才团队项目资助[黔科合平台人才(2016)5613\5677]。
关键词 FE3O4纳米颗粒 聚乙二醇 BOX-BEHNKEN效应面法 体外释药 光热控释 Fe3O4 nanoparticles polyethylene glycol Box-Behnken response surface method in vitro release photothermal controlled release
作者简介 赵青,女,硕士研究生,研究方向:靶向制剂与造影材料;通讯作者:杨畅,女,副教授,硕士生导师,研究方向:药物传递系统、靶向制剂、诊断试剂,Tel:15286039390E-mail:clare_yangchang@163.com.
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