PEG-derivative effectively modifies the characteristics of indomethacin-PLGA microspheres destined to intra-articular administration

Abstract

The aim of this study was to obtain biodegradable indomethacin microspheres for intra-articular administration in rheumatoid arthritis, where angiogenic processes are involved. Indomethacin concentrations to achieve an anti-angiogenic effect would be five-times higher than an anti-inflammatory. Microspheres were prepared by solvent evaporation using PLGA. Indomethacin is a poor water-soluble drug with it being possible that dissolved and non-dissolved drug co-exist within the polymeric matrix resulting in rapid release. To control this release, an oil-PEG-derivative was incorporated, producing changes in morphology, crystallinity and indomethacin release. To minimize the amount of microspheres administered, a two-factor five-level central rotable composite 2² + star design was employed with two independent variables: indomethacin percentage and PEG-derivative percentage. The optimum formulation showed mean encapsulation efficiency of 94.3 ± 2.2% and released 7.99 ± 0.25 µg indomethacin/day/mg microspheres for 21 days. A dose of 20–50 mg of this formulation could be appropriate to achieve both anti-angiogenic and anti-inflammatory effects. Preliminary cytotoxicity studies performed in rat splenocytes showed an adequate cell viability.

Key Words: :

• Microspheres
• PLGA/PEG-derivative
• intra-articular
• indomethacin
• rheumatoid arthritis