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

Molecules

Bowen Sui¹  Hui Xu³  Jian Jin¹  Jingxin Gou³  Jingshuo Liu¹  Xing Tang³  Yu Zhang³  Jinghua Xu²  Hongfeng Zhang² 

[1] Department of Pharmaceutics, College of Pharmacy Sciences, Jilin University, Changchun 130021, Jilin, China;School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China;Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China

关键词: miktoarm-star copolymer;    conjugate;    doxorubicin;    pH-responsive drug release;    drug delivery;   

DOI  :  10.3390/molecules190811915

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.