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）组成的水凝胶经历热敏和不连续的体积相变（即，在接近33.5 ℃的温度下，体积塌陷），这在刺激敏感生物材料如生物化学机械和药物递送装置的开发中是有意义的。然而，NIPAAm的神经毒性可能不比丙烯酰胺强多少，而丙烯酰胺已知会在实验动物中产生周围神经病变。然而，这是讨论NIPAAm凝胶在上述生物材料中的潜在用途的一个很大的障碍。因此，我们进行了动物实验，以评估皮下注射NIPAAm凝胶后的毒性。在食物和水的摄入量、体重和自发活动方面，观察到单体注射组和对照组之间的显著差异（根据Student’s t检验的统计分析，“风险”小于1%或5%）。此外，单体给药导致肾脏重量显著增加和脾脏重量降低。在血液检查中未观察到显著差异，但单体倾向于导致GOT和GPT水平升高。相比之下，给予凝胶的动物和对照动物之间的这些毒性指标没有显著差异。组织学观察显示，注射凝胶周围的组织炎症，直到3或4天，虽然在6天后达到完全治愈。从单体处理组获得的结果与以前的研究一致，其中每个都表明NIPAAm单体的神经毒性，但在方法上与我们的研究不同。然而，与对照实验相比，NIPAAm凝胶在毒性指标方面没有差异。从这些结果，我们推测，与单体相比，凝胶具有很小的毒性。然而，还需要进一步仔细的实验才能得出结论。

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.