Animal Experiments to Assess Toxicity Following Subcutaneous Administration of N-Isopropylacrylamide Gels Having Biochemo-Mechanical Function

由n -异丙基丙烯酰胺（NIPAAm）组成的水凝胶在接近33.5℃的温度下经历了热敏和不连续的体积相变（即体积崩塌），这对于开发刺激敏感的生物材料（如生化机械和药物输送装置）很有意义。然而，NIPAAm的神经毒性可能不会比丙烯酰胺强多少，而丙烯酰胺已经在实验动物中产生周围神经病变。然而，这对于讨论NIPAAm凝胶在上述生物材料中的潜在用途是一个很大的障碍。因此，我们进行了动物实验来评估皮下给药NIPAAm凝胶的毒性。注射单体组和对照组在食物和水摄入量、体重和运动活动方面存在显著差异（根据学生t检验的统计分析，“风险”小于1%或5%）。此外，单体给药使肾脏重量显著增加，脾脏重量显著减少。在血液检查中没有发现显著差异，但单体倾向于导致GOT和GPT水平升高。相比之下，凝胶给药和对照动物在这些毒性指标上没有显著差异。组织学观察显示，注射凝胶周围的组织炎症持续到3或4天，尽管6天后完全治愈。从单体处理组得到的结果与以往的研究结果一致，每个研究都表明NIPAAm单体的神经毒性，但在研究方法上与我们的研究不同。但与对照实验相比，NIPAAm凝胶在毒性指标上没有差异。根据这些结果，我们推测凝胶与单体相比毒性较小。然而，为了得出结论，还需要进一步仔细的实验。

Hydrogels consisting of N-Isopropylacrylamide (NIPAAm) undergo a thermosensitive and discontinuous volume-phase transition (I.e., volume collapse) at a temperature close to 33.5 ℃, which is of interest in the development of stimulus-sensitive biomaterials such as biochemo-mechanical and drug-delivery devices. However, NIPAAm, the neurotoxicity of which may not be much stronger than acrylamide, and acrylamide have been known to produce peripheral neuropathy in experimental animals. Nevertheless, this is a large barrier for discussing potential uses of NIPAAm gels in the aforementioned biomaterials. Thus, we performed animal experiments to assess toxicity following subcutaneous administration of NIPAAm gels.Significant differences (with a "risk" less than 1% or 5%, according to a statistical analysis by Student's t-test) between the monomer-injected and control groups were observed in the food and water intakes, body weight, and locomotor activity. Also, the monomer administration produced a significant increase in kidney weight and a decrease in spleen weight. No significant differences were seen in blood examinations, but the monomer tended to cause an increase in GOT and GPT levels. In contrast, there were no significant differences in these toxicity indicators between the gel administered and control animals. Histological observations showed an inflammation of the tissue around the gel injected until 3 or 4 days, although a complete cure was attained after 6 day.The results obtained from the monomer-treated groups are consistent with those of previous studies, each of which indicated the neurotoxicity of NIPAAm monomer but were different in the methodology from our study. However, NIPAAm gels produce no differences in toxicity indicators under comparison with control experiments. From these results, we speculate that the gel has little toxicity compared with the monomer. However, further careful experiments are required in order to reach a conclusion.