Box-Behnken 设计优化的 TPGS 包被的载阿那曲唑牛血清白蛋白纳米粒。

Box-Behnken Design Optimized TPGS Coated Bovine Serum Albumin Nanoparticles Loaded with Anastrozole.

机构信息

Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER)-Raebareli, Lucknow, Uttar Pradesh 226002, India.

出版信息

Curr Drug Deliv. 2021;18(8):1136-1147. doi: 10.2174/1567201818666210202104810.

DOI:10.2174/1567201818666210202104810

PMID:33530907

Abstract

PURPOSE

In this study, a novel D-α-tocopheryl polyethylene glycol succinate (TPGS) modified bovine serum albumin (BSA) nanoparticles (NPs) were developed for delivery of Anastrozole (ANZ) which is optimized by Box-Behnken design (BBD). Fabricated TPGS-ANZ-BSA NPs were evaluated for their physicochemical and drug release characteristics.

METHODS

TPGS-ANZ-BSA NPs were prepared by desolvation thermal gelation method and the effects of critical process parameter (CPP) which are BSA amount, TPGS concentration and stirring speed on the critical quality attributes (CQA) such as % drug loading (%DL) and particle size were studied using BBD. TPGS-ANZ-BSA NPs were characterized using different spectroscopic techniques including UV-Visible and FTIR is used to confirm the entrapment of ANZ in BSA. DSC and PXRD revealed the amorphization of ANZ in the TPGS-ANZ-BSA NPs after freeze drying. Scanning electron microscopy (SEM) analysis was performed for the surface morphology analyses NPs. In vitro release studies were performed at pH 5.5 and pH 7.4 for 48h to mimic tumour microenvironment.

RESULTS

The BBD optimized TPGS-ANZ-BSA NPs showed 107 nm particle size with %DL 8.5± 0.5%. The spectroscopic and thermal characterizations revealed the successful encapsulation of ANZ inside the NPs. The TPGS-ANZ-BSA NPs were found to exhibit burst release at pH 5.5 and sustained release at pH 7.4. The short-term stability displayed no significant changes in physical properties TPGS-ANZ-BSA NPs at room temperature for a period one month.

CONCLUSION

The BBD optimized TPGS-ANZ-BSA nanoparticles showed enhanced physiochemical properties for ANZ and potential candidates for anticancer agent drugs delivery.

摘要

目的

本研究采用 Box-Behnken 设计（BBD）优化，开发了一种新型 D-α-生育酚聚乙二醇琥珀酸酯（TPGS）修饰的牛血清白蛋白（BSA）纳米粒（NPs）用于 delivery 阿那曲唑（ANZ）。制备的 TPGS-ANZ-BSA NPs 对其理化性质和药物释放特性进行了评价。

方法

采用去溶剂热凝胶化法制备 TPGS-ANZ-BSA NPs，通过 BBD 研究 BSA 量、TPGS 浓度和搅拌速度等关键工艺参数（CPP）对关键质量属性（CQA），如药物载量（%DL）和粒径的影响。采用紫外可见分光光度法和傅里叶变换红外光谱法（FTIR）对载药纳米粒进行了不同光谱技术的表征，以确认 ANZ 包埋在 BSA 中。差示扫描量热法（DSC）和粉末 X 射线衍射（PXRD）表明，冷冻干燥后，ANZ 在 TPGS-ANZ-BSA NPs 中呈非晶态。采用扫描电子显微镜（SEM）对纳米粒的表面形态进行了分析。在 pH 5.5 和 pH 7.4 下进行 48 小时的体外释放研究，以模拟肿瘤微环境。

结果

BBD 优化的 TPGS-ANZ-BSA NPs 粒径为 107nm，载药量为 8.5±0.5%。光谱和热特性分析表明，ANZ 成功包封在 NPs 内。TPGS-ANZ-BSA NPs 在 pH 5.5 时表现出突释，在 pH 7.4 时表现出持续释放。短期稳定性显示，在室温下放置一个月，TPGS-ANZ-BSA NPs 的物理性质没有明显变化。