A gelatin-g-poly(N-isopropylacrylamide) biodegradable in situ gelling delivery system for the intracameral administration of pilocarpine

In this study, the aminated gelatin was grafted with carboxylic end-capped poly(N-isopropylacrylamide) (PN) via a carbodiimide-mediated coupling reaction to fabricate biodegradable in situ forming delivery systems for intracameral administration of antiglaucoma medications. The chemical structure of the graft copolymers (GN) was confirmed by Fourier transform infrared (FUR) spectroscopy. When the feed molar ratio of NH2/COOH was 0.36, the grafting ratio, efficiency and degree of grafting, and weight ratio of PN to aminated gelatin was 25.6, 18.6%, 52.6%, and 1.9, respectively. As compared to PN, the GN samples possessed better thermal gelation ability and adherence, indicating remarkable phase transition properties. Under gelatinase degradation, the remaining weight of GN was significantly lower than those of PN at each time point from 8 h to 4 weeks. Cytocompatibility studies showed that the culture of anterior segment cells with both in situ forming gels does not affect proliferation and has little effect on inflammation. Higher encapsulation efficiency (similar to 62%) and cumulative release (similar to 95%) were achieved for GN vehicles, which was attributed to initial fast temperature triggered capture of pilocarpine and subsequent progressive degradation of gelatin network. In a rabbit glaucoma model, the performance of delivery carriers was evaluated by biomicroscopy, intraocular pressure (IOP), and pupil size change. Intracameral administration of pilocarpine using GN was found to be more effective than other methods such as instillation of eye drop and injection of free drug or PN containing drug in improving ocular bioavailability and extending the pharmacological responses (i.e., miosis and LOP lowering effect and preservation of corneal endothelial cell density). (C) 2011 Elsevier Ltd. All rights reserved.