基于两亲性聚己内酯-聚环氧乙烷三嵌段和星形二嵌段共聚物的胶束:在药物递送应用中的潜力。

Micelles based on amphiphilic PCL-PEO triblock and star-shaped diblock copolymers: Potential in drug delivery applications.

作者信息

Quaglia Fabiana, Ostacolo Luisanna, Nese Giuseppe, Canciello Mariarosaria, De Rosa Giuseppe, Ungaro Francesca, Palumbo Rosario, La Rotonda Maria Immacolata, Maglio Giovanni

机构信息

Department of Pharmaceutical and Toxicological Chemistry, University of Naples Federico II, 80131 Naples, Italy.

出版信息

J Biomed Mater Res A. 2008 Dec 1;87(3):563-74. doi: 10.1002/jbm.a.31804.

Abstract

In this work, the potential in drug nanodelivery of micelles made from poly(epsilon-caprolactone) (PCL) and poly (ethyleneoxide) (PEO) copolymers with triblock and star-diblock architectures was explored. Linear and 4-arm star-shaped PCL macromers with two or four --OH end groups were prepared by ring-opening polymerization of CL and condensed with alpha-methoxy-omega-carboxy-PEO. The resulting amphiphilic copolymers were characterized by (1)H NMR, size exclusion chromatography, and differential scanning calorimetry. Separate PCL and PEO crystalline phases were observed for both copolymers. Copolymers self-assembled in water giving critical association concentrations in the range 0.010-0.023 mg/mL. Micelles with a size of 32-45 nm were prepared by dialysis and characterized for hydrodynamic diameter and surface charge. Their potential as nanocarriers in drug delivery applications was evaluated too. Micelles were nontoxic to both Red blood cells and HeLa cells. Complement activation experiments indicated that micelles can escape the reticuloendothelial system once intravenously injected. Finally, a different uptake on HeLa cells was found for micelles obtained from triblock and star-shaped copolymers.

摘要

在这项工作中,研究了由具有三嵌段和星型二嵌段结构的聚(ε-己内酯)(PCL)和聚(环氧乙烷)(PEO)共聚物制成的胶束在药物纳米递送方面的潜力。通过CL的开环聚合制备了具有两个或四个-OH端基的线性和四臂星型PCL大分子单体,并与α-甲氧基-ω-羧基-PEO缩合。通过核磁共振氢谱(¹H NMR)、尺寸排阻色谱法和差示扫描量热法对所得的两亲性共聚物进行了表征。两种共聚物均观察到单独的PCL和PEO晶相。共聚物在水中自组装,临界缔合浓度范围为0.010 - 0.023 mg/mL。通过透析制备了尺寸为32 - 45 nm的胶束,并对其流体动力学直径和表面电荷进行了表征。还评估了它们作为药物递送应用中纳米载体的潜力。胶束对红细胞和HeLa细胞均无毒。补体激活实验表明,胶束静脉注射后可逃避网状内皮系统。最后,发现由三嵌段和星型共聚物获得的胶束对HeLa细胞的摄取情况不同。

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