Doxorubicin-polyphosphazene conjugate hydrogels for locally controlled delivery of cancer therapeutics

被引:108
作者
Chun, ChangJu [1 ]
Lee, Sun M. [1 ]
Kim, Chang W. [1 ]
Hong, Ki-Yun [1 ]
Kim, Sang Y. [2 ]
Yang, Han K. [3 ]
Song, Soo-Chang [1 ]
机构
[1] Korea Adv Inst Sci & Technol, Div Life Sci, Seoul 136791, South Korea
[2] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Otolaryngol Head & Neck Surg, Seoul 138736, South Korea
[3] Seoul Natl Univ, Coll Med, Dept Gen Surg, Seoul 110744, South Korea
关键词
Localization; Biodegradable; Thermosensitive; Polymer-doxorubicin conjugate; Hydrogel; Antitumor efficacy; BIODEGRADABLE THERMOSENSITIVE POLYMERS; AMINO-ACID ESTERS; DRUG-DELIVERY; BOUND DOXORUBICIN; SIDE-GROUPS; ADRIAMYCIN; DAUNORUBICIN; MECHANISMS; RESISTANCE; THERAPY;
D O I
10.1016/j.biomaterials.2009.05.031
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Poly(organophosphazene)-doxorubicin (DOX) conjugate bearing hydrophobic L-isoleucine ethyl ester (IleOEt) and hydrophilic alpha-amino-omega-methoxy-poly(ethylene glycol) with molecular weight of 550 Da (AMPEG 550) along with carboxylic acid as a functional group was synthesized to create a drug delivery system, which is based on locally injectable, biodegradable, and thermosensitive hydrogels. In addition to the evaluation of the in vitro and in vivo antitumor activities, the physicochemical properties, hydrolytic degradation, and DOX release profile of the poly(organophosphazene)-DOX conjugate were determined. The aqueous solution of the polymer-DOX conjugate showed a sol-gel transition behavior depending on temperature changes. Based on the in vivo antitumor activities of the locally injected poly(organophosphazene)-DOX conjugate into the tumor-induced nude mice, the conjugate hydrogel after the local injection at the tumor site was shown to inhibit tumor growth more effectively with less toxicity and much longer than doxorubicin and saline as controls, indicating that tumor active DOX from the conjugate hydrogel is released slowly over a longer period of time and effectively accumulated locally in the tumor sites. These results suggest that the poly(organophosphazene)-doxorubicin conjugates hold great potential for use in preclinical and clinical studies as single and/or combination therapies. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码:4752 / 4762
页数:11
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