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 µM and reaching 41% protection at 5 µM. An in situ thermoresponsive hydrogel (17% / poloxamer 407 and 0.1% Carbopol) with suitable properties for ophthalmic application was optimized with respect to gelation temperature (31.40 ± 0.36 °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 °C (2129 ± 24 Pa∙s), 6-fold increase in the permeation, and prolonged release over 6 h.