Development of Meloxicam-chitosan magnetic nanoconjugates for targeting rheumatoid arthritis joints: Pharmaceutical characterization and preclinical assessment on murine models

The primary aim of our study is to formulate the meloxicam loaded chitosan-magnetite nanoconjugates (MC-MNCs) for the magnetically targeted rheumatoid arthritis therapy with an anticipation to improve the drug efficacy through enhancing its regional bioavailability, reducing dose frequency and related toxicity. The chitosan-magnetite nanoconjugates was prepared by in-situ co-precipitation of FeSO4 and FeCl3 solution in basic medium subsequently cross-linked with chitosan in the presence of sodium tripolyphosphate. Meloxicam dispersion was co-loaded onto the chitosan-magnetite nanoconjugates yielding MC-MNCs. These nanoconjugates were characterized by diverse techniques for their morphological, physicochemical, magnetic, pharmaceutical and pharmacological properties. MC-MNCs were roughly spherical. DLS measurements confirm its mean hydrodynamic size (258 nm), polydispersity index (0.233) and zeta potential (25.6 mV). FT-IR spectroscopic investigations showed the functional integrity of meloxicam, while XRD measurements showed the crystalline nature of magnetite and meloxicam in MC-MNCs, respectively. The chitosan-coated magnetite nanoparticles (C-MNP) and MC-MNCs showed a magnetic susceptibility of 168 x 10(-5) and 110 x 10(-5) SI units, respectively. The encapsulation efficiency and loading capacity of meloxicam entrapped into MC-MNCs was found to be 82% and 13% respectively. The in-vitro meloxicam release in phosphate buffer saline (pH 7.4) showed an initial burst release effect and followed by a slow drug release pattern. Meloxicam release from the MC-MNCs followed the Michaelis-Menten kinetics, adopting a super case II transport mechanism. MC-MNCs was found sufficiently stable with no major visual changes. Murine models of inflammation and arthritis was used to test the pharmacological efficacy of MC-MNCs. Magnetically targeted drug delivery of MC-MNCs enhanced the anti-inflammatory effect and anti-arthritic activity on the carrageenan-induced paw oedema in adjuvant-induced arthritis models in rats when compared with other treatments without applied magnetic field. Considering the overall research analysis, it is concluded that the MC-MNCs could be used as a viable alternative to the conventional formulations of meloxicam to ease rheumatoid arthritis.