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制备一种γ-聚谷氨酸-D-半乳糖酯化衍生物-顺铂复合物[Poly(γ-glutamic acid)-D-galactose esterifiable derivative-Cisplatin Complex Compound,γ-D+-DDP],并考察其体内靶向性。通过生物发酵获得大分子γ-聚谷氨酸[Poly(γ-glutamic acid),γ-PGA],利用酸降解得到可以作为药物载体的小分子γ-聚谷氨酸;利用凝胶色谱柱检验小分子γ-聚谷氨酸的分子量;利用HPLC检测释放的游离顺铂含量,得到复合物在小鼠体内靶向性分布情况;利用HE组织切片染色,观察脏器受损伤情况及靶向分布。实验结果表明:成功获得γ-聚谷氨酸-D-半乳糖酯化衍生物-顺铂复合物,该复合物载药率达9.4%～10.2%;HPLC结果表明注射复合物后,肝脏中药物显著增加而肾脏中药物分布明显减少,大大减少了肾毒性,肝靶向作用明显。因此,γ-聚谷氨酸-D-半乳糖酯化衍生物-顺铂复合物是一种有效的具有肝靶向性的抗肿瘤药物,具有潜在的临床应用价值;通过生物发酵获得的γ-聚谷氨酸可用于药物载体,赋予药物新的特点。
A γ-glutamic acid-D-galactose esterifiable derivative-Cisplatin Complex Compound, γ-D + -DDP] Investigate its in vivo targeting. Poly (γ-glutamic acid), γ-PGA] was obtained by biofermentation, and then the small molecule γ-polyglutamic acid which can be used as a drug carrier was obtained by acid degradation. By using the gel column test The molecular weight of small molecule γ-polyglutamic acid; the free cisplatin released by HPLC was measured to obtain the targeted distribution of the compound in mice; the damage of the organ and the targeted distribution were observed by HE tissue section staining . The experimental results show that the drug-loading rate of the compound is 9.4% -10.2%, and the compound of γ-polyglutamic acid-D-galactosyl ester derivative and cisplatin is successfully obtained. HPLC results show that in the liver Drug significantly increased the distribution of drugs in the kidney significantly reduced, greatly reducing the nephrotoxicity, liver-specific role. Therefore, the γ-polyglutamic acid-D-galactoside-esterified derivative-cisplatin compound is an effective liver-targeting anti-tumor drug with potential clinical application value; γ - Polyglutamic acid can be used as a drug carrier, giving the drug new features.