The effect of hyperbranched polyglycerol coatings on drug delivery using degradable polymer nanoparticles

被引：122

作者：

Deng, Yang ^{[1
]}

Saucier-Sawyer, Jennifer K. ^{[1
]}

Hoimes, Christopher J. ^{[2
]}

Zhang, Junwei ^{[3
]}

Seo, Young-Eun ^{[1
]}

Andrejecsk, Jillian W. ^{[1
]}

Saltzman, W. Mark ^{[1
]}

机构：

[1] Yale Univ, Dept Biomed Engn, New Haven, CT 06511 USA

[2] Yale Univ, Dept Med Oncol, New Haven, CT 06520 USA

[3] Yale Univ, Dept Chem & Environm Engn, New Haven, CT 06511 USA

来源：

BIOMATERIALS | 2014年 / 35卷 / 24期

关键词：

Surface coating; Nanoparticles; Camptothecin; Hyperbranched polyglycerol; Polylactic acid; BIOLOGICAL EVALUATION; CANCER-THERAPY; SYSTEMS;

D O I：

10.1016/j.biomaterials.2014.04.038

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

A key attribute for nanoparticles (NPs) that are used in medicine is the ability to avoid rapid uptake by phagocytic cells in the liver and other tissues. Poly(ethylene glycol) (PEG) coatings has been the gold standard in this regard for several decades. Here, we examined hyperbranched polyglycerols (HPG) as an alternate coating on NPs. In earlier work, HPG was modified with amines and subsequently conjugated to poly(lactic acid) (PLA), but that approach compromised the ability of HPG to resist non-specific adsorption of biomolecules. Instead, we synthesized a copolymer of PLA HPG by a one-step esterification. NPs were produced from a single emulsion using PLA HPG: fluorescent dye or the anti-tumor agent camptothecin (CPT) were encapsulated at high efficiency in the NPs. PLA HPG NPs were quantitatively compared to PLA PEG NPs, produced using approaches that have been extensively optimized for drug delivery in humans. Despite being similar in size, drug release profile and in vitro cytotoxicity, the PLA-HPG NPs showed significantly longer blood circulation and significantly less liver accumulation than PLA PEG. CPT-loaded PLA HPG NPs showed higher stability in suspension and better therapeutic effectiveness against tumors in vivo than CPT-loaded PLA PEG NPs. Our results suggest that HPG is superior to PEG as a surface coating for NPs in drug delivery. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：6595 / 6602

页数：8

共 33 条

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