聚乙二醇-聚酰胺-胺的合成、表征及其人角膜上皮细胞毒性研究.pdfVIP

聚乙二醇-聚酰胺-胺的合成、表征及其人角膜上皮细胞毒性研究 1 1 1 1 1 1,2* 周绣棣 ，曲 涛 ，慕宏杰 ，魏俊花 ，陈大全 ，孙考祥 1 烟台大学药学院，烟台 264005 ；2 山东绿叶制药有限公司，烟台 264005 ） [摘要] 目的：研究不同相对分子质量聚乙二醇（PEG ）修饰不同代数树枝状大分子聚酰 胺-胺（PAMAM ）得到的产物，测定其对人体角膜上皮细胞（HCECs ）的毒性。方法：采用硝 基苯氯甲酸酯（p-NPC ）将单甲氧基聚乙二醇（mPEG ，相对分子质量为750, 2 000, 5 000 ）活化 成PEG碳酸酯，对第4 ，5代PAMAM大分子进行修饰；目标产物用FT-IR 、1H-NMR进行结构表 征；采用WST-8法考察PEG修饰对PAMAM 的人角膜上皮细胞（HCECs ）毒性的影响。结果： PAMAM经较低浓度PEG修饰后，对HCECs 的毒性减弱不明显，经较高浓度PEG修饰后，对 HCECs减毒明显减弱，不同相对分子质量的PEG修饰对PAMAM 的减毒作用无明显差异。结论： 经PEG修饰后，可以降低PAMAM对HCECs 的毒性，作为新型眼部给药载体具有良好的前景。 [关键词] 聚乙二醇；聚酰胺-胺；角膜上皮细胞；毒性 Synthesis, characterization of PEG-PAMAM and their cytotoxicity on human corneal epithelial cells * ZHOU Xiu-di, QU Tao, MU Hong-jie, WEI Jun-hua, CHEN Da-quan, SUN Kao-xiang (School of Pharmacy, Yantai University, Yantai 264005, China) [Abstract] Objective: To study the cytotoxic effects of PAMAM G4,G5 modified by each PEG(Methoxy polyethylene glycol) on human corneal epithelial cells(HCECs). Method: The PEG (MW=750， 2000 ，5000) were activated to carbonates by p-nitrophenyl chloroformate, and modified 1 the PAMAM G4 ，G5. The products were characterizated by FT-IR, H-NMR. And then, we detected their toxicity to HCECs by WST-8. Result: Compared to PAMAM, modified PAMAM with PEG manifested lower reduced cytotoxicity at low concentritions, but obviously higher at high concentritions. But their reduced cytotoxicity have little difference at each molecular weight PEG modified PAMAM. Conclusion: PAMAM modified by PEG seem to be a very promising drug delivery syste