Ophthalmic In Situ Nanocomposite Gel for Delivery of a Hydrophobic Antioxidant

The topical administration of in situ hydrogels for ocular pathologies is a promising application strategy for providing high effectiveness and patient compliance. Curcumin, a natural polyphenol, possesses all the prerequisites for successful therapy of ophthalmic diseases, but unfortunately its physicochemical properties hurdle the practical use. Applying a composite in situ thermoresponsive hydrogel formulation embedded with polymer nanoparticles is a potent strategy to overcome all the identified drawbacks. In the present work we prepared uniform spherical nanoparticles (296.4 +/- 3.1 nm) efficiently loaded with curcumin (EE% 82.5 +/- 2.3%) based on the biocompatible and biodegradable poly-(lactic-co-glycolic acid). They were thoroughly physicochemically characterized in terms of FTIR, SEM, TGA, and DLS, in vitro release following Fickian diffusion (45.62 +/- 2.37%), and stability over 6 months. Their lack of cytotoxicity was demonstrated in vitro on HaCaT cell lines, and the potential for antioxidant protection was also outlined, starting from concentrations as low as 0.1 mu M and reaching 41% protection at 5 mu M. An in situ thermoresponsive hydrogel (17% w/v poloxamer 407 and 0.1% Carbopol) with suitable properties for ophthalmic application was optimized with respect to gelation temperature (31.40 +/- 0.36 degrees C), gelling time (8.99 +/- 0.28 s) upon tears dilution, and gel erosion (90.75 +/- 4.06%). Upon curcumin-loaded nanoparticle embedding, the in situ hydrogels demonstrated appropriate pseudoplastic behavior and viscosity at 35 degrees C (2129 +/- 24 Pa center dot s), 6-fold increase in the permeation, and prolonged release over 6 h.