Hydrogels are among the most used polymer–drug systems, polysaccharide-based materials presenting many advantages to be used for controlled release applications. Gellan maleate/NIPAm hydrogels are hydrophilic swelling matrixes that were originally developed for biomedical applications as controlled release dosage forms. The purpose of this study is to explore the ability of gellan maleate/NIPAm thermoreversible hydrogels for ophthalmic applications as ocular inserts. Studied hydrogels were synthesized by free radical grafting/polymerization of unsaturated esters (gellan maleate) with N-isopropylacrylamide (NIPAm) and N,N′-methylenebisacrylamide as cross-linker. They are evaluated for swelling degree, in vitro inclusion and release of drugs (adrenaline and chloramphenicol) and in vivo biocompatibility. The hydrogel is shown to be a temperature-responsive material with a LCST close to 36 °C. The swelling properties and the release of biologically active compounds occur when polymer conformation changes determining phase transition at LCST. Gellan-based hydrogels present reproducible responses to alternation between ambient temperature and human body one. The stability and biocompatibility were evaluated in vitro and in vivo. Tissue response to implantation of hydrogel was determined by histological analysis (haematoxylin–eosin–methylene blue and periodic acid–Schiff). A thin fibrous capsule was observed around the implanted hydrogels. No necrosis, calcification and acute inflammatory reaction were noted. Successful preliminary results were obtained for ophthalmic applications.

中文翻译：

---

热敏马来酸结冷胶/N-异丙基丙烯酰胺水凝胶：作为眼部插入物的初步“体外”和“体内”评估

水凝胶是最常用的聚合物-药物系统之一，基于多糖的材料具有许多优点，可用于控释应用。马来酸结冷胶/NIPAm 水凝胶是亲水性溶胀基质，最初作为控释剂型用于生物医学应用。本研究的目的是探索马来酸结冷胶/NIPAm 热可逆水凝胶作为眼部插入物在眼科应用中的能力。研究的水凝胶是通过不饱和酯（马来酸结冷胶）与 N-异丙基丙烯酰胺（NIPAm）和 N,N'-亚甲基双丙烯酰胺作为交联剂的自由基接枝/聚合合成的。对它们的溶胀度、体外药物（肾上腺素和氯霉素）的包含和释放以及体内生物相容性进行评估。水凝胶是一种温度响应材料，LCST 接近 36°C。当聚合物构象改变决定 LCST 的相变时，就会发生溶胀特性和生物活性化合物的释放。基于结冷胶的水凝胶对环境温度和人体之间的变化具有可重复的响应。在体外和体内评价稳定性和生物相容性。通过组织学分析（苏木精-伊红-亚甲蓝和高碘酸-希夫）确定组织对水凝胶植入的反应。在植入的水凝胶周围观察到薄的纤维囊。未见坏死、钙化及急性炎症反应。眼科应用取得了成功的初步结果。当聚合物构象改变决定 LCST 的相变时，就会发生溶胀特性和生物活性化合物的释放。基于结冷胶的水凝胶对环境温度和人体之间的变化具有可重复的响应。在体外和体内评价稳定性和生物相容性。通过组织学分析（苏木精-伊红-亚甲蓝和高碘酸-希夫）确定组织对水凝胶植入的反应。在植入的水凝胶周围观察到薄的纤维囊。未见坏死、钙化及急性炎症反应。眼科应用取得了成功的初步结果。当聚合物构象改变决定 LCST 的相变时，就会发生溶胀特性和生物活性化合物的释放。基于结冷胶的水凝胶对环境温度和人体之间的变化具有可重复的响应。在体外和体内评价稳定性和生物相容性。通过组织学分析（苏木精-伊红-亚甲蓝和高碘酸-希夫）确定组织对水凝胶植入的反应。在植入的水凝胶周围观察到薄的纤维囊。未见坏死、钙化及急性炎症反应。眼科应用取得了成功的初步结果。基于结冷胶的水凝胶对环境温度和人体之间的变化具有可重复的响应。在体外和体内评价稳定性和生物相容性。通过组织学分析（苏木精-伊红-亚甲蓝和高碘酸-希夫）确定组织对水凝胶植入的反应。在植入的水凝胶周围观察到薄的纤维囊。未见坏死、钙化及急性炎症反应。眼科应用取得了成功的初步结果。基于结冷胶的水凝胶对环境温度和人体之间的变化具有可重复的响应。在体外和体内评价稳定性和生物相容性。通过组织学分析（苏木精-伊红-亚甲蓝和高碘酸-希夫）确定组织对水凝胶植入的反应。在植入的水凝胶周围观察到薄的纤维囊。未见坏死、钙化及急性炎症反应。眼科应用取得了成功的初步结果。在植入的水凝胶周围观察到薄的纤维囊。未见坏死、钙化及急性炎症反应。眼科应用取得了成功的初步结果。在植入的水凝胶周围观察到薄的纤维囊。未见坏死、钙化及急性炎症反应。眼科应用取得了成功的初步结果。