Suzuki Takahisa, Tsunoda Shigeru, Yamashita Kota, Kuwahara Toshie, Ando Mitsuru, Tabata Yasuhiko, Obama Kazutaka
Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Laboratory of Biomaterials, Department of Regeneration Science and Engineering, Institute for Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
Pharmaceutics. 2022 Nov 25;14(12):2601. doi: 10.3390/pharmaceutics14122601.
The objective of this study was to develop a new preparation method for cisplatin (CDDP)-incorporated gelatin hydrogels without using chemical crosslinking nor a vacuum heating instrument for dehydrothermal crosslinking. By simply mixing CDDP and gelatin, CDDP-crosslinked gelatin hydrogels (CCGH) were prepared. CDDP functions as a crosslinking agent of gelatin to form the gelatin hydrogel. Simultaneously, CDDP is incorporated into the gelatin hydrogel as a controlled release carrier. CDDP's and anticancer efficacy after incorporation into CCGH was evaluated. In the system, the CDDP was released gradually due to CCGH degradation with an initial burst release of approximately 16%. CDDP metal-coordinated with the degraded fragment of gelatin was released from CCGH with maintaining the anticancer activity. After intraperitoneal administration of CCGH, CDDP was detected in the blood circulation while its toxicity was low. Following intraperitoneal administration of CCGH in a murine peritoneal dissemination model of human gastric cancer MKN45-Luc cell line, the survival time was significantly prolonged compared with free CDDP solution. It is concluded that CCGH prepared by the CDDP-based crosslinking of gelatin is an excellent sustained release system of CDDP to achieve superior anticancer effects with minimal side effects compared with free CDDP solution.
本研究的目的是开发一种新的制备方法，用于制备含顺铂（CDDP）的明胶水凝胶，该方法既不使用化学交联，也不使用用于脱水热交联的真空加热仪器。通过简单地将CDDP与明胶混合，制备了CDDP交联明胶水凝胶（CCGH）。CDDP作为明胶的交联剂形成明胶水凝胶。同时，CDDP作为控释载体被掺入明胶水凝胶中。评估了CDDP掺入CCGH后的释放情况和抗癌效果。在该体系中，由于CCGH降解，CDDP逐渐释放，初始突释约为16%。与明胶降解片段金属配位的CDDP从CCGH中释放出来，并保持抗癌活性。腹腔注射CCGH后，血液循环中可检测到CDDP，但其毒性较低。在人胃癌MKN45-Luc细胞系的小鼠腹膜播散模型中腹腔注射CCGH后，与游离CDDP溶液相比，生存时间显著延长。结论是，通过基于CDDP的明胶交联制备的CCGH是一种优异的CDDP缓释系统，与游离CDDP溶液相比，能以最小的副作用实现优异的抗癌效果。
