Development and In Vivo Evaluation of Pectin Based Enteric Coated Microparticles Loaded with Mesalamine and Saccharomyces boulardii for Management of Ulcerative Colitis.

Abstract

Mesalamine is the first-line choice of drug for ulcerative colitis management. However, due to the nontargeted delivery of mesalamine, it shows side effects. The possible impact of mesalamine can be improved by coated microparticles in combination with S. boulardii for targeted delivery to the colon with the prevention of unwanted side effects. In this work, pectin-based mesalamine and S. boulardii loaded microparticles were prepared by dehydration technique and coated by an oil-in-oil solvent evaporation method and characterized by Scanning electron microscopy (SEM), X-ray diffraction, and zeta analysis. 2, 4, 6-Trinitrobenzenesulfonic acid was used for the induction of colitis. The anti-inflammatory effects of coated microparticles on Caco-2 cells were assessed by the determination of interleukin (IL)-8 concentration. In addition, the impact of coated microparticles on the concentration of colonic enzymes, including myeloperoxidase (MPO), lipid peroxides, and glutathione (GSH), were also evaluated. Moreover, hematological parameters, including white blood cell (WBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), were assessed. SEM data revealed that all the prepared coated microparticles had an almost spherical shape. The X-ray powder diffraction analysis of uncoated and coated microparticles showed maximum stability without any interaction. The particle size of uncoated and coated microparticles was 9.14 and 15.61 μm, respectively. The zeta potential of uncoated and coated microparticles was observed to be -26.78 and -29.36 mV, respectively. The prepared coated microparticles decreased the levels of lipid peroxides, MPO, and GSH significantly in colitis. In the Caco-2 cell culture model, the concentration of IL-8 is decreased significantly. The hematological observations confirmed that the prepared formulation showed a promising decrease in the levels of WBC, CRP, and ESR in diseased animals. Animal experiments revealed that cellulose acetate phthalate coated microparticles of mesalamine and S. boulardii significantly improved the colitis disease conditions of Wistar rats. Hence, cellulose acetate phthalate-coated microparticles of mesalamine and S. boulardii could be recommended as adjuvant therapy to achieve a synergistic effect in the management of UC. Lay summary Mesalamine is the drug of choice for the management of ulcerative colitis (UC), which inhibits mediators responsible for inflammation. We investigated the in vivo effects of cellulose acetate phthalate-coated microparticles of mesalamine with Saccharomyces boulardii (probiotic) for their efficacy against UC. Our findings evidenced that the combination of mesalamine with S. boulardii showed a synergistic effect in the 2,4,6- trinitrobenzene sulfonic acid-induced colitis model by reducing the inflammation and maintains the macroscopic features. From the observed results, it can be concluded that S. boulardii can be used to enhance the individual drug's effect in the therapeutic management of UC.