Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, Japan.
Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
J Control Release. 2014 Feb 28;176:1-7. doi: 10.1016/j.jconrel.2013.12.021. Epub 2013 Dec 27.
We previously reported that the EGFR2R-lytic hybrid peptide has cytotoxic and anti-tumor activities both in vitro and in vivo. In this study, to improve the peptide pharmacokinetics and its anti-tumor activity after intravenous injection, we prepared biodegradable gelatin hydrogel nanoparticles as the delivery system of peptide. The complex is formed through the electrostatic interaction between the cationic peptide and anionic gelatin. In vitro release studies confirmed that the peptide was released from the complex in phosphate-buffered saline (PBS) solution containing fetal bovine serum at 37°C within 48h, whereas little release was observed in PBS solution. In vivo release studies indicated that the anti-tumor activity of the complex was more effective than that of peptide treatment alone, and high tumor accumulation of the peptide was observed in the mice treated with the complex. Furthermore, the plasma area under the concentration curve (AUC) and half-life (T1/2) values of the complex were higher than those of the peptide treatment alone, respectively. These results demonstrate that the rate of peptide release was controlled by the gelatin, and that the complex had a longer circulation time and enhanced its anti-tumor activity in vivo.
我们之前曾报道过，EGFR2R 溶瘤混合肽在体外和体内均具有细胞毒性和抗肿瘤活性。在这项研究中，为了改善肽的药代动力学特性并提高其静脉注射后的抗肿瘤活性，我们制备了可生物降解的明胶水凝胶纳米颗粒作为肽的递送系统。该复合物是通过阳离子肽与阴离子明胶之间的静电相互作用形成的。体外释放研究证实，在 37°C 的含胎牛血清的磷酸盐缓冲盐水（PBS）溶液中，肽在 48 小时内从复合物中释放，而在 PBS 溶液中几乎没有释放。体内释放研究表明，该复合物的抗肿瘤活性比单独使用肽治疗更有效，并且在用该复合物治疗的小鼠中观察到肽的高肿瘤蓄积。此外，复合物的血浆浓度-时间曲线下面积（AUC）和半衰期（T1/2）值均高于单独使用肽治疗的相应值。这些结果表明，肽的释放速率受明胶控制，并且该复合物具有更长的循环时间，并增强了其体内抗肿瘤活性。
