Nimbolide loaded sustained release microparticles as single-dose formulations for effective management of arthritis

Abstract

At present, sustained-release formulations have gained immense interest in drug development for improving the pharmacokinetic and pharmacodynamic properties of drugs. Nimbolide (NMB), one of the active constituents of the Neem tree (Azadirachta indica), has been studied for its anti-carcinogenic, anti-fibrotic, and anti-inflammatory properties, but it has poor pharmacokinetic issues. This study aims for preparing an intra-articularly injectable NMB-PLGA microparticle formulation (NMB MPs) that releases NMB in a sustained fashion once localized in joints for the treatment of arthritis. The formulation was characterized by scanning electron microscope, infrared spectroscopy, and in vitro drug release profiles. The MPs were spherical as evidenced by microscopic images with a mean diameter of 9.17 ± 2.75 μm. With the drug loading of 28% of NMB, the entrapment efficiency was 71.22 ± 3.53%. The formulated MPs could extend the drug release up to 62.25 ± 6.58%in 33 days in the in vitro conditions. The in vivo therapeutic effect of NMB MPs (single dose) was investigated in comparison to NMB free drug (weekly doses) in the rat model of Complete Freund's Adjuvant (CFA) induced arthritis. The anti-arthritic activity was evaluated based on knee swelling, X-ray analysis of knee joints, histopathology scoring, and expression of various essential proteins. The observed superior protective effects can be attributed to the sustained release of NMB from NMB MPs that facilitated the maintenance of therapeutic drug levels. In conclusion, NMB MPs can be a useful injectable delivery system for enhancing therapeutic efficiency in treating joint diseases.