The purpose of this study was to develop a novel pH-sensitive hydrogel which was used to regulate the acute radiation syndrome (ARS). The hydrogel was fabricated by grafting polycaprolactone onto methacrylic acid copolymer (MAC-g-PCL). Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (¹H NMR) confirmed the obtaining of MAC-g-PCL hydrogel. The hydrogel was pH-sensitive, at pH 1.2, it was compact hydrogel, but at pH7.4, it was dissolved solution. Its inner 3D morphology was observed by scanning electron microscope (SEM). Cell experiments indicated that the MAC-g-PCL hyrogel was out of cytotoxicity. The release profile of amifostine showed that small amount drug release in simulated gastric fluid (pH 1.2) and burst release in simulated intestinal fluid (pH 7.4). Thus, the pH-sensitive hydrogels could protect amifostine from enzymatic degradation in acidic stomach and deliver effectively in the intestine. The radioprotective efficacy was determined by peripheral complete blood parameters and 30-day survival study in mice acutely exposed to 4 Gy γ-ray total body irradiation. Results suggested that oral administration MAC-g-PCL/Ami before total body irradiation protected the mice from hematopoietic ARS and enhanced their survival. Furthermore, in vivo bio-distribution studies indicated that the drug could be sustained delivered at intestinal tract and entered the bloodstream. These results demonstrated that oral administration of amifostine hydrogel provided effective radioprotection to reduce the ARS injury.

本研究的目的是开发一种新型的 pH 敏感水凝胶，用于调节急性辐射综合征 (ARS)。通过将聚己内酯接枝到甲基丙烯酸共聚物（MAC-g-PCL）上来制造水凝胶。傅里叶变换红外光谱 (FTIR) 和核磁共振 ( ¹H NMR）证实了 MAC-g-PCL 水凝胶的获得。水凝胶对pH敏感，在pH 1.2时，它是致密的水凝胶，但在pH7.4时，它是溶解溶液。通过扫描电子显微镜 (SEM) 观察其内部 3D 形态。细胞实验表明 MAC-g-PCL 水凝胶没有细胞毒性。氨磷汀的释放曲线表明在模拟胃液 (pH 1.2) 中少量药物释放和在模拟肠液 (pH 7.4) 中突释。因此，pH 敏感水凝胶可以保护氨磷汀免受酸性胃中的酶促降解，并在肠道中有效递送。通过外周全血参数和急性暴露于 4 Gy γ 射线全身照射的小鼠的 30 天存活研究确定辐射防护功效。结果表明，在全身照射前口服 MAC-g-PCL/Ami 可保护小鼠免受造血 ARS 的影响并提高其存活率。此外，体内生物分布研究表明，该药物可以在肠道内持续释放并进入血液。这些结果表明，口服氨磷汀水凝胶可提供有效的辐射防护以减少 ARS 损伤。