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基于多臂星形聚乳酸-羟基乙酸共聚物-聚乙二醇嵌段共聚物的阿霉素负载胶束：臂数对药物递送的影响

Doxorubicin-loaded micelles based on multiarm star-shaped PLGA-PEG block copolymers: influence of arm numbers on drug delivery.

作者信息

Ma Guilei, Zhang Chao, Zhang Linhua, Sun Hongfan, Song Cunxian, Wang Chun, Kong Deling

机构信息

The Tianjin Key Laboratory of Biomaterials, Institute of Biomedical Engineering, Peking Union Medical College & Chinese Academy of Medical Sciences, Tianjin, 300192, China.

Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, 55455, USA.

出版信息

J Mater Sci Mater Med. 2016 Jan;27(1):17. doi: 10.1007/s10856-015-5610-4. Epub 2015 Dec 16.

DOI:10.1007/s10856-015-5610-4
PMID:26676863
Abstract

Star-shaped block copolymers based on poly(D,L-lactide-co-glycolide) (PLGA) and poly(ethylene glycol) (PEG) (st-PLGA-PEG) were synthesized with structural variation on arm numbers in order to investigate the relationship between the arm numbers of st-PLGA-PEG copolymers and their micelle properties. st-PLGA-PEG copolymers with arm numbers 3, 4 and 6 were synthesized by using different cores such as trimethylolpropane, pentaerythritol and dipentaerythritol, and were characterized by nuclear magnetic resonance and gel permeation chromatography. The critical micelle concentration decreased with increasing arm numbers in st-PLGA-PEG copolymers. The doxorubicin-loaded st-PLGA-PEG micelles were prepared by a modified nanoprecipitation method. Micellar properties such as particle size, drug loading content and in vitro drug release behavior were investigated as a function of the number of arms and compared with each other. The doxorubicin-loaded 4-arm PLGA-PEG micelles were found to have the highest cellular uptake efficiency and cytotoxicity compared with 3-arm PLGA-PEG micelles and 6-arm PLGA-PEG micelles. The results suggest that structural tailoring of arm numbers from st-PLGA-PEG copolymers could provide a new strategy for designing drug carriers of high efficiency. Structural tailoring of arm numbers from star shaped-PLGA-PEG copolymers (3-arm/4-arm/6-arm-PLGA-PEG) could provide a new strategy for designing drug carriers of high efficiency.

摘要

合成了基于聚（D，L-丙交酯-共-乙交酯）（PLGA）和聚乙二醇（PEG）的星形嵌段共聚物（st-PLGA-PEG），其臂数具有结构变化，以研究st-PLGA-PEG共聚物的臂数与其胶束性质之间的关系。通过使用不同的核心，如三羟甲基丙烷、季戊四醇和二季戊四醇，合成了臂数为3、4和6的st-PLGA-PEG共聚物，并通过核磁共振和凝胶渗透色谱对其进行了表征。st-PLGA-PEG共聚物的临界胶束浓度随着臂数的增加而降低。通过改进的纳米沉淀法制备了载有阿霉素的st-PLGA-PEG胶束。研究了胶束性质，如粒径、载药量和体外药物释放行为与臂数的关系，并进行了相互比较。结果发现，与3臂PLGA-PEG胶束和6臂PLGA-PEG胶束相比，载有阿霉素的4臂PLGA-PEG胶束具有最高的细胞摄取效率和细胞毒性。结果表明，对st-PLGA-PEG共聚物的臂数进行结构调整可为设计高效药物载体提供新策略。对星形PLGA-PEG共聚物（3臂/4臂/6臂-PLGA-PEG）的臂数进行结构调整可为设计高效药物载体提供新策略。

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本文引用的文献

[1]
Utilization of H-bond interaction of nucleobase Uralic with antitumor methotrexate to design drug carrier with ultrahigh loading efficiency and pH-responsive drug release.

Regen Biomater. 2014-10-20

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