Fabrication and evaluation of lipid nanoparticulates for ocular delivery of a COX-2 inhibitor

Context: The unique physiological limitations of the eye have been assigned as reason of low bioavailability by conventional drug delivery systems. There is need of such drug carriers, which ensure improved bioavailability as well as patient compliance upon instillation into the eye. Objective: The present investigation deals with development of solid lipid nanoparticles (SLNs) containing celecoxib (CXB) for treatment of ophthalmic inflammations. Materials and methods: The SLNs were formulated by melt-emulsion sonication and low temperature-solidification process and evaluated for particle size, surface morphology, physicochemical properties, percentage drug incorporation efficiency, in vitro drug release, in vitro trans-corneal permeation, in vivo efficacy in ocular inflammation, stability study and gamma scintigraphy study to assess the residence of solid lipid nanoparticles over ocular surfaces. Results: The SLNs were spherical and the optimized formulation had particle size of 198.777.5nm, which is quite suitable for ocular applications. The maximum entrapment efficiency of 92.46 +/- 0.07% was achieved for formulation SLN 20. The permeation across the cornea was also significantly better than aqueous suspension (8.21 +/- 0.67 versus 4.61 +/- 0.71) at p<0.05. Discussion and conclusion: The SLN formulations demonstrated improved performance of entrapped CXB while mitigating the key parameters of ocular inflammation in rabbits. The particulate formulations have exhibited prolonged retention over ocular surfaces as evident from results of gamma scintigraphy using Tc-99m labeled SLNs.