聚(2-乙基-2-噁唑啉)-聚乳酸胶束的血液相容性和细胞相容性研究

doi:10.5246/jcps.2014.10.086

中国药学(英文版) ›› 2014, Vol. 23 ›› Issue (10): 674-680.DOI: 10.5246/jcps.2014.10.086

聚(2-乙基-2-噁唑啉)-聚乳酸胶束的血液相容性和细胞相容性研究

马淑金¹, 李艳芳², 赵勇¹, 周艳霞¹, 李晋文¹, 高雅杰¹, 李雨书¹, 李馨儒^1*, 刘艳^1*, 王杏林³

1. 北京大学医学部药学院药剂学系, 北京 100191
2. 北京大学第三医院中心实验室, 北京 100191
3. 天津药物研究院释药技术与药代动力学国家重点实验室, 天津 300193

收稿日期:2014-04-11 修回日期:2014-05-15 出版日期:2014-10-31 发布日期:2014-05-20
通讯作者: Tel.: 86-10-82801508
基金资助:
National Natural Science Foundation of China (Grant No. 81172990), the National Key Science Research Program of China (Grant No. 973 Program, 2009CB930300), Innovation Team of Ministry of Education (Grant No. BMU20110263) and the Open Project Program of State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research.

Hemocompatibility and cytocompatibility of diblock copolymer poly(2-ethyl-2-oxazoline)-poly(D,L-lactide)-based micelles

Shujin Ma¹, Yanfang Li², Yong Zhao¹, Yanxia Zhou¹, Jinwen Li¹, Yajie Gao¹, Yushu Li¹, Xinru Li^1*, Yan Liu^1*, Xinglin Wang³

1. Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Sciences Center, Beijing 100191, China
2. Central Lab, Peking University Third Hospital, Beijing 100191, China
3. State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China

Received:2014-04-11 Revised:2014-05-15 Online:2014-10-31 Published:2014-05-20
Contact: Tel.: 86-10-82801508
Supported by:
National Natural Science Foundation of China (Grant No. 81172990), the National Key Science Research Program of China (Grant No. 973 Program, 2009CB930300), Innovation Team of Ministry of Education (Grant No. BMU20110263) and the Open Project Program of State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research.

摘要/Abstract

摘要：

合成的二嵌段共聚物聚(2-乙基-2-噁唑啉)-聚乳酸(PEOz-PLA)可自组装形成胶束, 其在药物输送领域的应用与日俱增。然而, 其与血液和细胞之间的相互作用迄今未知。本研究拟对PEOz-PLA胶束的血液相容性和细胞相容性进行评价, 为PEOz-PLA胶束的潜在应用提供数据支持。通过溶血、凝血时间、血小板激活以及与白蛋白的相互作用评价了PEOz-PLA胶束的血液相容性。结果表明, PEOz-PLA胶束的血液相容性良好。SRB的实验结果表明, PEOz-PLA胶束与KBv细胞孵育后并未出现明显的细胞毒性, 显示出良好的细胞相容性。总之, PEOz-PLA胶束是血液和细胞相容的药物载体, 可用于静脉给药。

关键词: 血液相容性, 细胞相容性, PEOz-PLA胶束, 溶血, 凝血, 血小板激活, 蛋白吸附

Abstract:

A synthetic diblock copolymerpoly(2-ethyl-2-oxazoline)-poly(D,L-lactide) (PEOz-PLA) can self-assemble into micelles with an increased efficiency of drug delivery. However, the interactions of blood-micelles and cell-micelles remain unclear. In the present study, we aimed to assess the hemocompatibility and cytocompatibility of PEOz-PLA micelles in order to clarify its potentials as carriers for drug delivery. Blood compatibility of the micelles was evaluated by hemolysis analysis, coagulation test, platelet activation investigation and assessment of their interaction with protein. The results revealed that PEOz-PLA micelles had a favorable blood compatibility. In addition, PEOz-PLA micelles showed a good cytocompatibility through SRB assay, presenting only negligible cytotoxicity when incubated with KBv cells. Taken together, PEOz-PLA micelles could be used as a hemocompatible andcytocompatible drug carrier for intravenous administration.

Key words: Hemocompatibility, Cytocompatibility, PEOz-PLA micelles, Hemolysis, Blood clotting, Platelet activation, Protein adsorption

中图分类号:

R944

Supporting:

马淑金, 李艳芳, 赵勇, 周艳霞, 李晋文, 高雅杰, 李雨书, 李馨儒, 刘艳, 王杏林. 聚(2-乙基-2-噁唑啉)-聚乳酸胶束的血液相容性和细胞相容性研究[J]. 中国药学(英文版), 2014, 23(10): 674-680.

Shujin Ma, Yanfang Li, Yong Zhao, Yanxia Zhou, Jinwen Li, Yajie Gao, Yushu Li, Xinru Li, Yan Liu, Xinglin Wang. Hemocompatibility and cytocompatibility of diblock copolymer poly(2-ethyl-2-oxazoline)-poly(D,L-lactide)-based micelles[J]. Journal of Chinese Pharmaceutical Sciences, 2014, 23(10): 674-680.

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聚(2-乙基-2-噁唑啉)-聚乳酸胶束的血液相容性和细胞相容性研究

Hemocompatibility and cytocompatibility of diblock copolymer poly(2-ethyl-2-oxazoline)-poly(D,L-lactide)-based micelles

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