叶酸接枝的姜黄素前药树枝状大分子衍生物的合成及性能研究

Synthesis and performance study of folate-conjugated curcumin prodrug dendrimer derivative

目的制备一种叶酸(FA)接枝的前药型树枝状大分子聚酰胺-胺(PAMAM)衍生物FA-聚乙二醇(PEG)-PAMAM-姜黄素(Cur)并考察其性能。方法通过酰胺化反应将疏水性药物Cur和靶向分子FA键合到树枝状大分子PAMAM表层,通过1H NMR表征其结构,通过凝胶渗透色谱测定其相对分子质量,并计算Cur和FA的接枝数,从而验证了接枝产物的形成;将树枝状大分子衍生物PAMAM-Cur和FA-PEG-PAMAM-Cur作为载体,考察了其对Cur载药量的增加程度并考察其释药行为;选用人肝癌肿瘤细胞HepG2考察目标产物FA-PEG-PAMAM-Cur的肿瘤靶向性。结果每个树枝状大分子PAMAM表层平均键合了2.9个Cur分子和2.8个FA分子;FA-PEG-PAMAM-Cur作为载体提高了Cur的载药量,并且提高了肿瘤细胞对药物的摄取能力。结论树枝状大分子衍生物FA-PEG-PAMAM-Cur在作为抗肿瘤药物传递系统方面具有广阔前景。

Objective To design and synthesize a folate-conjugated prodrug dendrimer folic acid-polyethylene glycol-polyamine-curcumin（FA-PEG-PAMAM-Cur）.Methods The hydrophobic drug Cur and targeting molecule FA were conjugated to the surface of PAMAM via the amidation reaction.The dendrimer conjugate was characterized in terms of relative molecular mass and structure using gel permeation chromatography and proton nuclear magnetic resonance spectroscopy,respectively.The drug loading and release profiles of the dendrimer（PAMAM-Cur and FA-PEG-PAMAM-Cur） were also investigated;the targeting capability of these conjugates was analyzed in the human hepatocellular carcinoma cell line（HepG2）.Results Each dendrimer PAMAM surface was conjugated with 2.9 Cur molecules and 2.8 FA molecules.FA-PEG-PAMAM-Cur exhibited enhanced Cur loading and cellular uptake of drug.Conclusion The FA-PEG-PAMAM-Cur would be a useful addition to the nanoparticulate Cur delivery systems available.