Inhibition of endotoxin-induced uveitis by methylprednisolone acetate nanosuspension in rabbits

Purpose: In this study, nanoformulations of methylprednisolone acetate (MPA) were formulated by using a copolymer of poly(ethylacrylate, methyl-methacrylate and chlorotrimethyl-ammonioethyl methacrylate) to study their impacts on the inhibition of inflammatory symptoms in rabbits with endotoxin-induced uveitis (EIU). Methods: A modified quasiemulsion solvent diffusion technique was used for the preparation of the nanoparticles. The drug-release profiles and physicochemical characteristics of the nanoformulations were studied by means of X-ray crystallography, differential scanning calorimetry, and Fourier transform infrared spectroscopy. Particle-size analysis yielded mean diameters of approximately 380, 460, and 580 (nm) for copolymer nanoparticles at the ratios of 1:2.5,1:5, and 1:10, respectively. Major clinical symptoms of EIU (e.g., morphologic changes, leukocytes numbers, and protein levels within the aqueous humor) were examined. Results: Upon the physicochemical characterizations, no crystal changes or chemical interactions were observed for the copolymer nanoparticles. The 1:2.5 ratio of drug polymer resulted in the most controlled release of MPA. The in vivo examinations revealed that the endotoxin-induced inflammation can be inhibited by the copolymer nanosuspension more significantly than by the microsuspension of MPA itself in the rabbits with EIU. Conclusions: Based on our findings, we suggest that the copolymer nanosuspension may favor the localized, controlled ocular delivery of MPA for the prevention of inflammatory symptoms in ocular diseases.