Inhibition of endotoxin-induced uveitis by methylprednisolone acetate nanosuspension in rabbits.
OBJECTIVE
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.
Adibkia
Khosro
K
Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran.
Omidi
Yadollah
Y
Siahi
Mohammad R
MR
Javadzadeh
Ali R
AR
Barzegar-Jalali
Mohammad
M
Barar
Jaleh
J
Maleki
Nasrin
N
Mohammadi
Ghobad
G
Nokhodchi
Ali
A
D000180:Acrylic Resins; D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D001082:Aqueous Humor / Q000166:cytology / Q000378:metabolism; D002152:Calorimetry, Differential Scanning; D004337:Drug Carriers; D004731:Endotoxins; D007958:Leukocyte Count; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000077555:Methylprednisolone Acetate; D053758:Nanoparticles; D010316:Particle Size; D011817:Rabbits; D017550:Spectroscopy, Fourier Transform Infrared; D013535:Suspensions; D014605:Uveitis / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D014961:X-Ray Diffraction
D000180:Acrylic Resins; D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D004731:Endotoxins; D013535:Suspensions; C050528:Eudragit RS; D000077555:Methylprednisolone Acetate; D008775:Methylprednisolone