中文摘要：

目的分别制备了聚乙二醇（PEG）修饰的第四代（C,4）和第五代（G5）聚酰胺一胺（PAMAM）树枝状大分子一甲氨蝶呤（MTX）复合物，考察其体外释药特性．方法通过酰胺键将功能化PEG与PAMAM表面氨基连接，考察PEG化PAMAM的溶血毒性；制备PAMAM-PEG／MTX复合物，测定最大复合量；考察复合物在不同缓冲溶液及血浆中的体外释药行为及不同储存条件下的稳定性。结果通过PEG化修饰，每分子G4PAMAM分别连接了11，21和29个PEG分子；每分子G5PAMAM分别连接了16，30和37个PEG分子，随着PAMAM的PEG化程度提高，其溶血毒性显著减小，复合MTX的量增多。PAMAM—PEG／Mrrx在10和1mmol·L-1（pH7．4）的Tris—HCl缓冲溶液中表现出缓释效果，但加入NaCl后释放加快：放置3个月后，复合物中MTX含量略有下降，药物释放未发生变化。结论与PAMAM相比，PAMAM—PEG的溶血毒性显著降低，并具有一定缓释效果，有望成为一种新型给药载体材料。

英文摘要：

OBJECTIVE To synthesize poly （ ethylene glycol） （PEG） grafted polyamidoamine （PAMAM） dendrimer and investigate the effect of PEGylated PAMAM on in vitro release of methotrexate （ MTX ） in complex. METHODS Poly （ ethylene glycol） with the average weight 5 000 was combined to the fourth and fifth generation PAMAM via amide bond. Hemolytic toxicity concerning the PEGylated PAMAM was evaluated. UV and HPI.C was employed to monitor the in vitro release of MTX from PEgylated PAMAM in different buffers. RESULTS PE（,vlated PAMAM exhibited lower hemolytic toxicit） than non-PEGylated PAMAM. The ability of PEGy laled PAMAM to complex with MTX was increased with the degree of PEGylated. In ritro release rate of MTX from the eomplex much slower than that of the free MTX, which, however, was effected by the ionic strength of the buffer. CONCLUSION PEGylated PAMAM could be a potential drug delivery carrier for methotrexate with a sustained re.lease behavior under suitable conditions.