Journal
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
Volume 81, Issue 3, Pages 582-590Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejpb.2012.04.008
Keywords
Antitumor activity; Poly(organophosphazene); Thermosensitive hydrogel; Polymer-drug conjugate; Stability of camptothecin
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Funding
- Korea Institute of Science and Technology (KIST)
- Ministry of Education, Science and Technology in Korea
- National Research Council of Science & Technology (NST), Republic of Korea [2E2271] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2010-50197, 전06A1101] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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The objective of this study is to develop an effective polymer therapeutics involving camptothecin (CPT) with enhanced efficacy and lessened systemic side-toxicity for cancer treatment. Polymer-CPT conjugates (PCCs), which consisted of CPT-20-glycinate and poly(organophosphazene) bearing carboxylic acid, were synthesized, characterized for physicochemical properties, in vitro degradation and CPT release behaviors from the PCC, and evaluated their anticancer activity. The aqueous solutions of all these PCCs showed a thermo-responsive sol-gel transition behavior for injectable application near room temperature. The CPT incorporated into the hydrogel was proven to be stable in vitro over 15 days. The in vitro cytotoxicity of the PCC was verified to be effective against four kinds of human cancer cell lines. The in vivo anticancer activity study with HT-29 colon cancer cell xenografted mice showed that the intratumorally injected PCC hydrogel inhibited the tumor growth more effectively relative to CPT alone (-29% vs. 130% in tumor size). Crown Copyright (C) 2012 Published by Elsevier B.V. All rights reserved.
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