The development of advanced drug delivery systems with extensively sustained release and multiple functions is highly imperative for effective attenuation of the degradation of ocular extracellular matrix that is associated with inflammatory glaucoma. Here, the generation of amine-terminated polyamidoamine dendrimers in an injectable biodegradable thermogel is demonstrated to be important for achieving prolonged drug release profiles and potent anti-inflammatory effects. Among various generations (Gx, x = 0, 1, 3, 5), third-generation G3 is proved as the most effective material for optimizing the synergistic effects of gelatin and poly(N-isopropylacrylamide) and generating a thermogel with the highest biodegradation resistance, the best drug encapsulation/extended-release performance, and the best ability to reduce the elevated expression of inflammatory molecules. A pharmacotherapy based on intracameral injection of thermogels coloaded with pilocarpine and ascorbic acid results in effective alleviation of progressive glaucoma owing to the anti-inflammatory activity and long-acting drug release (above a therapeutic level of 10 µg mL-1 over 80 days) of thermogels, which simultaneously suppress inflammation and stimulate regeneration of stromal collagen and retinal laminin. These findings on the dendritic effects of rationally designed injectable biomaterials with potent anti-inflammatory effects and controlled drug release demonstrate great promise of their use for pharmacological treatment of progressive glaucoma.

中文翻译：

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注射型生物降解热凝胶对炎性青光眼相关的细胞外基质降解药物治疗的树突效应。

具有广泛持续释放和多种功能的先进药物递送系统的开发对于有效减轻与炎性青光眼有关的眼细胞外基质的降解非常重要。在此，在可注射的可生物降解的热凝胶中胺端基的聚酰胺酰胺树状聚合物的生成被证明对于延长药物释放曲线和有效的抗炎作用非常重要。在第三代（Gx，x = 0、1、3、5）中，第三代G3被证明是最有效的材料，可优化明胶和聚N-异丙基丙烯酰胺的协同作用，并产生具有最高生物降解性的热凝胶耐药性，最佳的药物封装/延长释放性能，并具有减少炎症分子高表达的最佳能力。基于前房内注射与毛果芸香碱和抗坏血酸共载的热凝胶的药物疗法，由于抗炎活性和长效药物释放（在80天内超过10 µg mL-1的治疗水平），可有效缓解进行性青光眼。热凝胶，可同时抑制炎症并刺激基质胶原和视网膜层粘连蛋白的再生。这些关于合理设计的可注射生物材料具有有效抗炎作用和可控药物释放的树突状作用的研究结果表明，将其用于进行性青光眼的药理学治疗具有广阔的前景。基于前房内注射与毛果芸香碱和抗坏血酸共载的热凝胶的药物疗法，由于抗炎活性和长效药物释放（在80天内超过10 µg mL-1的治疗水平），可有效缓解进行性青光眼。热凝胶，可同时抑制炎症并刺激基质胶原和视网膜层粘连蛋白的再生。这些关于合理设计的可注射生物材料具有有效抗炎作用和可控药物释放的树突状作用的研究结果表明，将其用于进行性青光眼的药理学治疗具有广阔的前景。基于前房内注射与毛果芸香碱和抗坏血酸共载的热凝胶的药物疗法，由于抗炎活性和长效药物释放（在80天内超过10 µg mL-1的治疗水平），可有效缓解进行性青光眼。热凝胶，可同时抑制炎症并刺激基质胶原和视网膜层粘连蛋白的再生。这些关于合理设计的可注射生物材料具有有效抗炎作用和可控药物释放的树突状作用的研究结果表明，将其用于进行性青光眼的药理学治疗具有广阔的前景。