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以生物发酵法获得的γ-聚谷氨酸经酸降解后得到小分子γ-聚谷氨酸(γ-PGA),柠檬酸(CA)通过酯化反应修饰其侧链羧基制备γ-聚谷氨酸-柠檬酸(γ-PGA-CA),再将顺铂(CDDP)与γ-PGA-CA上的羧基相结合制备得载药复合物γ-PGA-CA-CDDP,凝胶色谱法测定分子量,OPDA法测定载药量及有效结合率,透析法结合HPLC研究其对顺铂的缓释效果,MTT法检测复合物的体外抗肿瘤活性,采用新鲜兔血检测载体材料及复合物的溶血性。实验结果表明:成功获得γ-PGA-CA及γ-PGA-CA-CDDP,该复合物相对分子质量约为66k,有效结合率达65%,载药率达16%～20%,48 h时顺铂的累计释放率达到50%,MTT检测显示该复合物对肿瘤细胞具有良好的抑制效果,相对于游离顺铂具有较低的毒性,且无溶血性。因此,γ-PGA-CA可作为药物载体,γ-PGA-CA-CDDP具有潜在的临床应用价值。
Γ-polyglutamic acid (γ-PGA) is obtained after the γ-polyglutamic acid obtained by the bio-fermentation method is acid-degraded, and the carboxyl group of the side chain is modified by the esterification reaction to prepare γ-polyglutamic acid GGA-CA was used to prepare γ-PGA-CA-CDDP, which was prepared by combining γ-PGA-CA with CDDP and carboxyl groups on γ-PGA- Molecular weight, OPDA assay drug loading and effective binding rate, dialysis method combined with HPLC study of its sustained release of cisplatin, MTT assay of the compound in vitro antitumor activity, using fresh rabbit blood to detect the carrier material and the complex hemolysis Sex. The results showed that the relative molecular mass of the complex was about 66k, the effective binding rate was 65% and the drug loading rate was 16% -20%. The results showed that γ-PGA-CA and γ-PGA- The cumulative release rate of cisplatin reached 50%. MTT assay showed that the compound has a good inhibitory effect on tumor cells, which is less toxic than free cisplatin and has no hemolysis. Therefore, γ-PGA-CA can be used as a drug carrier, γ-PGA-CA-CDDP has potential clinical value.