Thermosensitive In Situ Gel of Nanosized Apremilast: Development and Assessment for Rheumatoid Arthritis Treatment

Abstract

Rheumatoid arthritis, in short called as RA, is a severe auto-immune condition characterized by thickening of the synovium joints, inflammation and soreness of joints, which subsequently destroys the articular structures. The drug used to treat RA requires the delivery of a formulation in intact form to synovial joints and release of a whole amount of medicine into synovial fluids. Apremilast is an anti-inflammatory drug used to treat arthritis, but its oral drug delivery is limited because of its low bioavailability and side effects. The nanoparticle-based in situ gel helps in prolonged formulation retention, which enables drug release within specific tissues such as cartilage and synovium. The purpose of this research is to formulate and assess the efficacy of a thermosensitive in situ gel of nanosized apremilast for managing RA. A total of nine apremilast- loaded nanoparticles in situ gels designated as F1–F9 were prepared with different ratios of Eudragit RSPO and polyvinyl alcohol using 25% w/v poloxamer 407 and poloxamer 188 as gelling agents. Among the various formulations, F5 showed a particle size of 119 nm, 80.8% EE, 27.54% DL, 37.5 ± 1.7∘C gelation temperature, 55 ± 1.0 second gelation time and 866 ± 13 cps viscosity, with a better in vitro drug release profile of 75.54% for 24 h by non-Fickian diffusion mechanism; thus, it was chosen as the most productive formulation. In an in vivo study in rats, the optimized formulation reduced inflammation at the test site. The developed nanoparticles in situ gel will be a novel carrier system for drugs used to treat RA.