线性聚乙烯亚胺(L-PEI)有许多应用,例如在药物制剂中,基因传递,和水处理。然而,由于仲胺基团的存在,L-PEI显示相对高的毒性和低的生物相容性。这里,各种有机酸酐用于修饰L-PEI以降低其毒性并增强其功能。我们选择了甲基丙烯酸酐,巴豆酸酐,马来酸酐,和琥珀酸酐改性L-PEI。使用1HNMR和FTIR光谱表征所得衍生物的结构,并使用比浊法和电泳迁移率测量在广泛的pH值范围内研究了它们在水溶液中的行为。荧光流过方法确定了聚合物对牛睑结膜的粘膜粘附特性。甲基丙烯酸酯化的L-PEI和巴豆酰化的L-PEI在pH7.4下显示出强的粘膜粘附性质,可能是由于与粘蛋白硫醇基团的共价键合。相比之下,由于pH高于其等电点,因此马来酰化和琥珀酰化的L-PEI的粘膜粘附性差,导致聚合物和粘蛋白之间的静电排斥。在人肺泡上皮细胞中,使用planaria和3-(4,5-二甲基噻唑-2-基)-2,5-二苯基-2H-四唑溴化物(MTT)细胞活力测定法评估了这些聚合物的毒性。此外,使用鼻塞粘膜刺激测定法评估聚合物的刺激性。结果表明,酸酐改性减轻了母体L-PEI的不利毒性作用。
Linear polyethylenimine (L-PEI) has numerous applications, such as in pharmaceutical formulations, gene delivery, and water treatment. However, due to the presence of secondary amine groups, L-PEI shows a relatively high toxicity and low biocompatibility. Here, various organic anhydrides were used to modify L-PEI to reduce its toxicity and enhance its functionality. We selected methacrylic anhydride, crotonic anhydride, maleic anhydride, and succinic anhydride to modify L-PEI. The structure of the resulting derivatives was characterized using 1H NMR and FTIR spectroscopies, and their behavior in aqueous solutions was studied using turbidimetric and electrophoretic mobility measurements over a broad range of pHs. A fluorescence flow through method determined the mucoadhesive properties of the polymers to the bovine palpebral
conjunctiva. Methacrylated L-PEI and crotonylated L-PEI showed strong mucoadhesive properties at pH 7.4, likely due to covalent bonding with mucin thiol groups. In contrast, maleylated and succinylated L-PEI were poorly mucoadhesive as the pH was above their isoelectric point, resulting in electrostatic repulsion between the polymers and mucin. The toxicity of these polymers was evaluated using in vivo assays with planaria and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) cell viability assay in human alveolar epithelial cells. Moreover, the irritancy of polymers was assessed using a slug mucosa irritation assay. The results demonstrated that anhydride modification mitigated the adverse toxicity effects seen for parent L-PEI.