Pharmaceutical Nanotechnology Nanoparticle-Based Topical Ophthalmic Formulations for Sustained Celecoxib Release

Celecoxib-loaded NPs were prepared from biodegradable polymers such as poly- e-caprolactone (PCL), poly(L-lactide) (PLA), and poly(D,L-lactide-co-glycolide) (PLGA) by spontaneous emulsification solvent diffusion method. Different concentrations of polymers, emulsifier, and cosurfactants were used for formulation optimization. Nanoparticles (NPs) were characterized regarding their particle size, PDI, zeta potential, shape, morphology, and drug content. Celecoxib-loaded NPs were incorporated into eye drops, in situ gelling system, and gel and characterized regarding their pH, viscosity, uniformity of drug content, in vitro release, and cytotoxicity. The results of optimized celecoxib-loaded PCL-, PLGA-, and PLA-NPs, respectively, are particle size 119 ± 4, 126.67 ± 7.08, and 135.33 ± 4.15 nm; zeta potential ? 22.43 ± 2.91, ? 25.46 ± 2.35, and ? 31.81 ± 2.54 mV; and encapsulation efficiency 93.44 ± 3.6%, 86.00 ± 1.67%, and 79.04 ± 2.6%. TEM analyses revealed that NPs have spherical shapes with dense core and distinct coat. Formulations possessed uniform drug content with pH and viscosity compatible with the eye. Formulations showed sustained release without any burst effect with the Higuchi non-Fickian diffusion mechanism. Cytotoxicity studies revealed that all formulations are nontoxic. Our formulations provide a great deal of flexibility to formulation scientist whereby sizes and zeta potentials of our NPs can be tuned to suit the need using scalable and robust methodologies. These formulations can thus serve as a potential drug delivery system for both anterior and posterior eye diseases. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:1036–1053, 2013