Dendritic Effects of Injectable Biodegradable Thermogels on Pharmacotherapy of Inflammatory Glaucoma-Associated Degradation of Extracellular Matrix.

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 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.