聚乙二醇修饰聚酰胺-胺的合成、表征及其人角膜上皮细胞毒性

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(PAM-AM)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。

Synthesis,characterization of PEG-PAMAM and their cytotoxicity in human corneal epithelial cells

Objective: To investigate the cytotoxic effects of PAMAMG4,G5 that are modified by polyethylene glycol(PEG) in human corneal epithelial cells(HCECs).Methods: Methoxy PEG(MW=750,2 000 and 5 000) were activated to carbonates by p-nitrophenyl chloroformate,and used to modify PAMAM for forming PAMAMG4,G5.The products were characterized by FT-IR and 1H-NMR.Then,we detected their toxicity to HCECs by WST-8 assay.Results: Compared to PAMAM,the modified PAMAM by PEG manifested lower cytotoxicity at low concentritions,but obviously higher at high concentritions.The reduction in cytotoxicity of the modified PAMAM by each molecular weight PEG little differed.Conclusion: The modified PAMAM by PEG seems to be a very promising drug delivery system due to their little cytotoxicity to human corneal epithelial cells.