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Self-Assembled Micelles Composed of Doxorubicin Conjugated Y-Shaped PEG-Poly(glutamic acid)2 Copolymers via Hydrazone Linkers

Authors :
Bowen Sui
Hui Xu
Jian Jin
Jingxin Gou
Jingshuo Liu
Xing Tang
Yu Zhang
Jinghua Xu
Hongfeng Zhang
Xiangqun Jin
Source :
Molecules, Vol 19, Iss 8, Pp 11915-11932 (2014)
Publication Year :
2014
Publisher :
MDPI AG, 2014.

Abstract

In this work, micelles composed of doxorubicin-conjugated Y-shaped copolymers (YMs) linked via an acid-labile linker were constructed. Y-shaped copolymers of mPEG-b-poly(glutamate-hydrazone-doxorubicin)2 and linear copolymers of mPEG-b-poly(glutamate-hydrazone-doxorubicin) were synthesized and characterized. Particle size, size distribution, morphology, drug loading content (DLC) and drug release of the micelles were determined. Alterations in size and DLC of the micelles could be achieved by varying the hydrophobic block lengths. Moreover, at fixed DLCs, YMs showed a smaller diameter than micelles composed of linear copolymers (LMs). Also, all prepared micelles showed sustained release behaviors under physiological conditions over 72 h. DOX loaded in YMs was released more completely, with 30% more drug released in acid. The anti-tumor efficacy of the micelles against HeLa cells was evaluated by MTT assays, and YMs exhibited stronger cytotoxic effects than LMs in a dose- and time-dependent manner. Cellular uptake studied by CLSM indicated that YMs and LMs were readily taken up by HeLa cells. According to the results of this study, doxorubicin-conjugated Y-shaped PEG-(polypeptide)2 copolymers showed advantages over linear copolymers, like assembling into smaller nanoparticles, faster drug release in acid, which may correspond to higher cellular uptake and enhanced extracellular/intracellular drug release, indicating their potential in constructing nano-sized drug delivery systems.

Details

Language :
English
ISSN :
14203049
Volume :
19
Issue :
8
Database :
Directory of Open Access Journals
Journal :
Molecules
Publication Type :
Academic Journal
Accession number :
edsdoj.58a180c9a7406b95a91181cecfa300
Document Type :
article
Full Text :
https://doi.org/10.3390/molecules190811915