Center for Biomaterials, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul, Republic of Korea.
Eur J Pharm Biopharm. 2012 Aug;81(3):582-90. doi: 10.1016/j.ejpb.2012.04.008. Epub 2012 Apr 24.
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).
本研究旨在开发一种有效的聚合物治疗药物，涉及喜树碱（CPT），以提高疗效和降低癌症治疗的全身毒性。聚合物-CPT 缀合物（PCC）由 CPT-20-甘氨酸和带有羧酸的聚（有机膦腈）组成，对其理化性质、体外降解和 PCC 中 CPT 的释放行为进行了表征，并评价了其抗癌活性。所有这些 PCC 的水溶液在接近室温的可注射应用中表现出热响应溶胶-凝胶转变行为。证明水凝胶中掺入的 CPT 在体外 15 天内稳定。对四种人癌细胞系的 PCC 体外细胞毒性验证表明，与单独使用 CPT 相比，PCC 水凝胶的抗肿瘤活性更有效（肿瘤大小分别为-29%和 130%）。
