Polypeptide-Based "Smart" Micelles for Dual-Drug Delivery: A Combination Study of Experiments and Simulations

被引：55

作者：

Chen, Lili ^{[1
]}

Jiang, Tao ^{[1
]}

Cai, Chunhua ^{[1
]}

Wang, Liquan ^{[1
]}

Lin, Jiaping ^{[1
]}

Cao, Xuguang ^{[1
]}

机构：

[1] E China Univ Sci & Technol, Shanghai Key Lab Adv Polymer Mat, Sch Mat Sci & Engn, Key Lab Ultrafine Mat,Minist Educ, Shanghai 200237, Peoples R China

来源：

ADVANCED HEALTHCARE MATERIALS | 2014年 / 3卷 / 09期

基金：

中国国家自然科学基金; 高等学校博士学科点专项科研基金;

关键词：

drug delivery; micelles; polypeptides; DPD simulation; BLOCK-COPOLYMER MICELLES; CONTROLLED-RELEASE; POLYMERIC MICELLES; PH; DOXORUBICIN; ASSEMBLIES; BEHAVIOR; DESIGN; VESICLES; TUMOR;

D O I：

10.1002/adhm.201300638

中图分类号：

R318 [生物医学工程];

学科分类号：

100103 [病原生物学];

摘要：

A dual-drug-loaded micelle is designed and constructed from a mixture of poly(propylene oxide)-b-poly(-benzyl-l-glutamate)-b-poly(ethylene glycol) (PPO-b-PBLG-b-PEG) triblock terpolymers and two model drugs, doxorubicin (DOX) and naproxen (Nap). In the micelles, the DOX is chemically linked to the PBLG backbones through an acid-cleavable hydrazone bond, whereas the Nap is physically encapsulated in the cores. The drug loading and releasing behaviors of the dual-drug-loaded micelles as well as single drug-loaded micelles (DOX-conjugated or Nap-loaded micelles) are studied. The structures of micelles are characterized by means of microscopies and dynamic light scattering, and further examined by dissipative particle dynamics (DPD) simulations. It is revealed that the micelles possess a core-shell-corona structure in which the PPO/Nap, PBLG/DOX, and PEG aggregate to form the core, shell, and corona, respectively. In vitro studies reveal that the release of DOX and Nap is pH- and thermosensitive. Such drug releasing behaviors are also examined by DPD simulations, and more information regarding the mechanism is obtained. In addition, the bio-related properties such as cellular uptake of the micelles and biocompatibility of the deliveries are evaluated. The results show that the dual-drug-loaded micelles are biocompatible at normal physiological conditions and retain the anti-cancer efficiency.

引用

页码：1508 / 1517

页数：10

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