聚山梨醇酯80修饰H102聚乳酸-羟基乙酸纳米粒的脑靶向性研究及细胞毒性评价

摘要

Objective: To study the brain targeting property of H102 loaded PEG-PLGA nanoparticles coated with polysorbate 80 (PS-H102-NP) and evaluate its cytotoxicity. Methods: After intravenous injection of H102-NP and PS-H102-NP in mice, plasma and brain tissue were collected at 5, 15, 30, 45, 60 and 120 min and drug concentration were determined by LC-MS. MTT assay was used to evaluate the cytotoxicity of polysorbate 80 and PS-H102-NP on BCECs. Results: PS-H102-NP showed long half life and mean residence time with a low clearance. The AUC of PS-H102-NP was 1.42 times higher than that of H102-NP. Polysorbate 80 below 2% showed good safety on BCECs and the toxicity of PS -H102 -NP was lower than that of H102-NP. Conclusion: PS-H102-NP show good brain targeting property and low cytotoxicity, providing experimental data to its application for the treatment of Alzheimer' s disease.%目的:考察聚山梨醇酯80修饰H102聚乳酸-羟基乙酸纳米粒(PS-H102-NP)的脑靶向性,并对其细胞毒性进行评价.方法:将H102-NP和PS-H102-NP两种制剂经小鼠静脉注射给药,采用LC-MS液质联用分析法测定给药后5、15、30、45、60和120 min时的血浆及脑组织中的药物浓度.采用MTT法评价聚山梨醇酯80和纳米粒对BCECs细胞的毒性.结果:PS-H 102-NP在脑内的半衰期和滞留时间延长,清除率下降,其AUC值是H102-NP的1.42倍.2％以下浓度的聚山梨醇酯80具有较佳的安全性,PS-H102-NP的毒性较H102-NP小.结论:PS-H 102-NP具有较好的脑靶向性和低毒性,为其应用于阿尔茨海默病的治疗提供实验依据.