Yin Lichen, Zhao Xin, Cui Liming, Ding Jieying, He Miao, Tang Cui, Yin Chunhua
State Key Laboratory of Genetic Engineering, Department of Pharmaceutical Sciences, School of Life Sciences, Fudan University, 220 Handan Road, Shanghai 200433, China.
Food Chem Toxicol. 2009 Jun;47(6):1139-45. doi: 10.1016/j.fct.2009.01.043.
The superporous hydrogel containing poly(acrylic acid-co-acrylamide)/O-carboxymethyl chitosan (O-CMC) interpenetrating polymer networks (SPH-IPN) that had been developed as an oral delivery vehicle for protein drugs was subject to cytotoxicity and genotoxicity testing, thus evaluating its biological safety in use. In a battery of cytotoxicity assays on RBL-2H3 and Caco-2 cells, the SPH-IPN caused minimal damage towards cell viability, lysosomal activity, and metabolic activity following both direct and indirect treatment. The SPH-IPN did not induce cell apoptosis or DNA breakage in the above cell lines; it did not increase micronucleus (MN) incidence in mouse bone marrow, either. Therefore, the SPH-IPN was preliminarily considered to be biocompatible and might be a safe carrier for protein drugs. In addition, using the HPLC method, residual acrylic acid, acrylamide, and glutaraldehyde in the SPH-IPN were quantified to be 1.4, 2.0, and below 0.2 ppm, respectively. Lack of these low molecular monomers and crosslinker that were mainly responsible for the toxicity provided evidence for the good biocompatibility of the SPH-IPN.
含有聚（丙烯酸 - 共 - 丙烯酰胺）/ O - 羧甲基壳聚糖（O - CMC）互穿聚合物网络（SPH - IPN）的超多孔水凝胶已被开发用作蛋白质药物的口服递送载体，该水凝胶进行了细胞毒性和遗传毒性测试，从而评估其使用中的生物安全性。在一系列针对RBL - 2H3和Caco - 2细胞的细胞毒性试验中，直接和间接处理后，SPH - IPN对细胞活力、溶酶体活性和代谢活性造成的损害最小。SPH - IPN在上述细胞系中未诱导细胞凋亡或DNA断裂；它也未增加小鼠骨髓中的微核（MN）发生率。因此，初步认为SPH - IPN具有生物相容性，可能是蛋白质药物的安全载体。此外，使用高效液相色谱法，测定出SPH - IPN中残留的丙烯酸、丙烯酰胺和戊二醛分别为1.4、2.0和低于0.2 ppm。缺乏这些主要导致毒性的低分子单体和交联剂为SPH - IPN良好的生物相容性提供了证据。
