Li Ruixin, Shu Chang, Wang Wei, Wang Xiaoliang, Li Hui, Xu Danke, Zhong Wenying
Department of Analytical Chemistry, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
Key Laboratory of Biomedical Functional Materials, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
J Pharm Sci. 2015 Jul;104(7):2266-75. doi: 10.1002/jps.24481. Epub 2015 May 15.
10-Hydroxy camptothecin (HCPT) has been proven to be a cell cycle-specific chemotherapeutic agent, which is a necessary choice to inhibit tumor residue growth and prevent tumor metastasis after surgery. But it suffers from light decomposition, poor solubility, relatively low bioavailability, and some side effects, which are the major obstacles toward its clinical use. Integration of hydrophobic HCPT with hydrophilic hydrogel is a facile approach to change the disadvantageous situation of HCPT. In this study, a novel supramolecular hydrogelator with improved synthetic strategy was triggered by chemical hydrolysis, and then self-assembled to hydrogel. Taking advantage of the high-equilibrium solubility of HCPT in hydrogelator solution, this hydrogel was utilized to load HCPT via encapsulation as an effective carrier. HCPT hydrogels were characterized by several techniques including transmission electronic microscopy, rheology, and UV spectroscopy. In vitro release experiment indicated HCPT hydrogel could maintain long term and sustained release of HCPT at high accumulated rate. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay showed that HCPT hydrogel had an optimized anticancer efficacy. Besides, with prominent physical properties of carrier, HCPT hydrogel possessed satisfactory stability, syringeability, and recoverability, demonstrating itself as a potential localized injectable drug delivery system.
10-羟基喜树碱(HCPT)已被证明是一种细胞周期特异性化疗药物,是抑制肿瘤残留生长和预防术后肿瘤转移的必要选择。但它存在光分解、溶解度差、生物利用度相对较低以及一些副作用等问题,这些是其临床应用的主要障碍。将疏水性的HCPT与亲水性水凝胶结合是改变HCPT不利状况的一种简便方法。在本研究中,一种具有改进合成策略的新型超分子水凝胶因子通过化学水解引发,然后自组装成水凝胶。利用HCPT在水凝胶因子溶液中的高平衡溶解度,该水凝胶被用作通过包封来负载HCPT的有效载体。通过包括透射电子显微镜、流变学和紫外光谱等多种技术对HCPT水凝胶进行了表征。体外释放实验表明,HCPT水凝胶能够以高累积率长期持续释放HCPT。3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐实验表明,HCPT水凝胶具有优化的抗癌效果。此外,凭借载体突出的物理性质,HCPT水凝胶具有令人满意的稳定性、可注射性和可恢复性,证明其自身是一种潜在的局部注射给药系统。