期刊
BIOMATERIALS
卷 30, 期 12, 页码 2349-2360出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2008.12.083
关键词
Biodegradable; Thermosensitive; Hydrogel; Polymer-drug conjugate; Paclitaxel; Antitumor activity
资金
- Ministry of Science and Technology in Korea [F104AA010007-07A0101-00110]
- National Research Council of Science & Technology (NST), Republic of Korea [2E21240] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2006-2008324] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
A poly(organophosphazene)-PTX conjugate was synthesized by a covalent ester linkage between M and carboxylic acid-terminated poly(organophosphazene), which can be readily modified by various hydrophobic, hydrophilic, and other functional substitutes. The physicochemical properties, hydrolytic degradation and PTX release behaviors of the polymer-PTX conjugate were characterized, in addition to the in vitro and in vivo antitumor activities. The aqueous solutions of these conjugates showed a sol-gel transition behavior that depended on temperature changes. The in vitro antitumor activity of the polymer-M conjugate was investigated by an MTT assay against human tumor cell lines. From the in vivo antitumor activity studies with tumor-induced (xenografted) nude mice, the polymer-paclitaxel conjugate hydrogels after local injection at the tumor site were shown to inhibit tumor growth more effectively and longer than paclitaxel and saline alone, indicating that the tumor-active paclitaxel from the polymer-PTX conjugate hydrogel is released slowly over a longer period of time and effectively accumulated locally in the tumor sites. These combined observations suggest that this poly (organophosphazene)-PTX conjugate holds promise for use in clinical studies as single and/or combination therapies. (C) 2009 Elsevier Ltd. All rights reserved.
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