JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS Volume 23, Number 5, 2007 © Mary Ann Liebert, Inc. DOI: 10.1089/jop.2007.0039 Inhibition of Endotoxin-Induced Uveitis by Methylprednisolone Acetate Nanosuspension in Rabbits KHOSRO ADIBKIA, 1,2,4 YADOLLAH OMIDI, 1,2, MOHAMMAD R. SIAHI, 1,2 ALI R. JAVADZADEH, 3 MOHAMMAD BARZEGAR-JALALI, 2,3 JALEH BARAR, 1,2 NASRIN MALEKI, 2 GHOBAD MOHAMMADI, 1,2 and ALI NOKHODCHI 2,5 ABSTRACT Purpose: In this study, nanoformulations of methylprednisolone acetate (MPA) were formu- lated by using a copolymer of poly(ethylacrylate, methyl–methacrylate and chlorotrimethyl– ammonioethyl methacrylate) to study their impacts on the inhibition of inflammatory symp- toms in rabbits with endotoxin-induced uveitis (EIU). Methods: A modified quasiemulsion solvent diffusion technique was used for the prepa- ration 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 inter- actions were observed for the copolymer nanoparticles. The 1:2.5 ratio of drug polymer re- sulted in the most controlled release of MPA. The in vivo examinations revealed that the en- dotoxin-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. 421 INTRODUCTION T HE LOCALIZED THERAPY of inflammatory eye diseases is of note owing to optimized im- pacts of drug with minimal side-effects. Most oc- ular diseases are classically treated with topical eye drops; however, such medications usually re- quire a frequent utilization of highly concentrated solutions, as physiologic responses of the eyes may quickly eliminate them from the eyes. 1 Thus, enormous efforts have, so far, been devoted to maximize the localized delivery and targeting of desired pharmaceuticals by the development of a de novo drug delivery system (DDS), including 1 Research Center for Pharmaceutical Nanotechnology, 2 Faculty of Pharmacy, and the 3 Drug Applied Research Cen- ter, Tabriz University of Medical Sciences, Tabriz, Iran. 4 School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran. 5 Medway School of Pharmacy, University of Greenwich, Kent, United Kingdom.