Self-Assembled Micelles from an Amphiphilic Hyperbranched Copolymer with Polyphosphate Arms for Drug Delivery
Self-Assembled Micelles from an Amphiphilic Hyperbranched Copolymer with Polyphosphate Arms for Drug Delivery
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用于药物输送的具有聚磷酸酯臂的两亲性超支化共聚物的自组装胶束
DOI：
10.1021/la1006988
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发表时间：
2010-07-06
期刊：
影响因子：
3.9
通讯作者：
Yan, Deyue
中科院分区：
文献类型：
--
作者：
Liu, Jinyao;Huang, Wei;Yan, Deyue
采用两步开环聚合法合成了一种新型的两亲性超支化多臂共聚物[H40-星星-（PLA-b-PEP-OH）]，并将其应用于药物缓释。首先，使用Boltorn H40作为大分子引发剂用于L-丙交酯的ROP以形成中间体（H40-star-PLA-OH）。然后，进一步引发乙基亚乙基磷酸酯的ROP以产生H 40-星星-（PLA-b-PEP-OH）。所得超支化多臂共聚物通过H-1、C-13和P-31 NMR、GPC和FTIR光谱进行表征。H40-星星-（PLA-b-PEP-OH）的两亲性结构使其能够在水中自组装成平均粒径为130 nm的胶束。通过甲基四氮唑测定、流式细胞术和共聚焦激光扫描显微镜测量，这些胶束的体外评价表明它们具有优异的生物相容性和有效的细胞摄取。研究了负载多柔比星的胶束对Hela人宫颈癌细胞系的增殖抑制，发现50%细胞生长所需的多柔比星剂量为1 μ g/mL。这些结果表明，H40-星星-（PLA-b-PEP-OH）胶束可用作安全、有前途的药物传递系统。
A novel type of amphiphilic hyperbranched multiarm copolymer [H40-star-(PLA-b-PEP-OH)] was synthesized through a two-step ring-opening polymerization (ROP) procedure and applied to drug delivery. First, Boltorn H40 was used as macroinitiator for the ROP of L-lactide to form the intermediate (H40-star-PLA-OH). Then, the ROP of ethyl ethylene phosphate was further initiated to produce H40-star-(PLA-b-PEP-OH). The resulting hyperbranched multiarm copolymers were characterized by H-1, C-13, and P-31 NMR, GPC, and FTIR spectra. Benefiting from the amphiphilic structure, H40-star-(PLA-b-PEP-OH) was able to self-assemble into micelles in water with an average diameter of 130 null. In vitro evaluation of these micelles demonstrated their excellent biocompatibility and efficient cellular uptake by methyl tetrazolium assay, flow cytometry, and confocal laser scanning microscopy measurements. Doxorubicin-loaded micelles were investigated for the proliferation inhibition of a Hela human cervical carcinoma cell line, and the Doxorubicin dose required for 50% cellular growth in was found to be I mu g/m L. These results indicate that H40-star-(PLA-b-PEP-OH) micelles can be used as safe, promising drug-delivery systems.