Anti-inflammatory and cytoprotective potentials of Meloxicam solid dispersions prepared by different techniques on lipopolysaccharide-stimulated RAW 264.7 macrophages

Abstract

The present study investigates the anti-inflammatory and cytoprotective potentials of a selective COX-II inhibitor, Meloxicam (MELOX) from solid-dispersions (SDs), using lipopolysaccharide (LPS)–stimulated RAW 264.7 macrophages cell line. MELOX/SDs were prepared by fusion (FM) & hot-melt-extrusion (HME) techniques using Soluplus/Lutrol F127 as mixed-polymers. SDs were physicochemically evaluated by SEM, XRD and solubility-testing. Viability of cell-growth was determined by MTT assay. Evaluation of inflammation was based on production of nitric oxide (NO), tumor necrosis factor-α (TNF-α) and prostaglandin E2 (PGE2). MELOX Solubility increased by 3- and 4- folds from SDs prepared by FM and HME, respectively, compared to pure drug. XRD/SEM analyses confirmed drug-dispersion within mixed-polymers. Exposure of normal-cells to different MELOX-treatments maintained the integrity of cell-growth. LPS-stimulated cells treated with MELOX/SDs exhibited higher viabilities compared to cells treated with pure MELOX. The prepared MELOX/SDs showed statistically stronger inhibition of inflammatory-mediators with respect to pure drug. Only, MELOX/SDs prepared by HME, successfully restored LPS-induced TNF-α level to that of normal-cells. SDs prepared by HME provided superior reduction of NO, TNF-α and PGE2, while maintaining normal cell-growth. The present study highlights the effect of SDs preparation techniques, on MELOX treatment performance.