Cyclosporine-Loaded Microspheres for Treatment of Uveitis: In Vitro Characterization and In Vivo Pharmacokinetic Study

A sustained intraocular level of immunosuppressive drug is desirable for the treatment of uveitis and other intraocular immune disorders. The objective of the present investigation was to assess the suitability of cyclosporine-loaded poly(lactic-co-glycolic acid) microspheres (CyS-PLGA-MS) to achieve this goal. A solvent-evaporation method was used in the preparation of CyS-PLGA-MS. These microspheres were characterized for drug loading, entrapment efficiency, and in vitro release by high-performance liquid chromatography, particle size by phase-contrast light microscopy and surface morphology by scanning electron microscopy. The 3H-CyS-PLGA-MS suspension was injected into the vitreous body of healthy rabbits, and the concentration of cyclosporine in various ocular tissues and blood at predetermined intervals was measured by a scintillation counting technique and the pharmacokinetic parameters were calculated. Intravitreous administration of 3H-CyS solution was conducted as the control. The CyS-PLGA-MS was produced, with drug-loading ranging from 11% to 16% and a high entrapment efficiency from 86% to 98%. Microspheres were discrete, spherical particles with a diameter of approximately 50 microm. The CyS was constantly and slowly released from microspheres in the in vitro release experiment. Compared with CyS solution, microspheres prolonged the release of CyS and maintained therapeutic CyS concentrations for at least 65 days in disease-related tissues such as the choroid-retina and iris-ciliary body. The percentage of CyS released in vitro correlated well with the CyS distribution rate in vivo. CyS-PLGA-MS, displaying sustained intraocular release of CyS and showing advantages over CyS solution, may meet clinical needs more efficiently.