Formulation and Optimization of Ligand Appended Chitosan-Ethyl Cellulose Microspheres for the Treatment of Inflammatory Bowel Disease

Abstract

Primary limitation in the drug therapy of inflammatory bowel disease (IBD) is failure to deliver the drug molecule selectively towards the inflamed cells. The aim of the present investigation was to develop resveratrol loaded ligand appended Chitosan-Ethyl Cellulose Microspheres for the treatment of IBD. Microparticulate drug delivery systems have led to progression in the therapeutic selectivity. In present investigation, resveratrol loaded microspheres were developed by applying spray drying technique which possesses biodegradable properties (chitosan) as well as control releasing properties (ethyl cellulose). Formulation parameters and processing variables were screened (using Plackett and Burman screening design) and considering significant parameters, formulation was further optimized systematically (using full factorial design). Though it enables the system to deliver the drug at the inflamed site, the greater part of the loaded drug is eliminated without imparting a beneficial effect. Hence, to overcome this limitation ligand appended chitosan-ethyl cellulose microspheres were prepared comprising of folate appended and peanut agglutinin. The ligand appended drug loaded microspheres were developed in order to achieve an active targeting and selective adhesion region. Folate (FA) and peanut agglutinin (PNA) were covalently bound to the surface of chitosan-ethyl cellulose microspheres and were characterized for local drug release in colon. In vitro studies of microspheres depict a premature release of drug in the stomach and small intestine. As enteric coating of microspheres is difficult to achieve, pellets were prepared. Drug release studies of microspheres loaded pellets revealed that the microspheres remained intact during the Pelletization process. In-vivo benefit for resveratrol loaded folate appended chitosanethyl cellulose microspheres and peanut agglutinin appended chitosan-ethyl cellulose microspheres were studied in oxazolone induced colitis rat models. Ligand appended microspheres shows an added improvement of the selectivity of bioadhesion towards inflamed cells which moderately results into better therapeutic efficiency. Ligand appended microspheres decreased neutrophil infiltration, MPO activity and the levels of inflammatory markers (i.e. TNF-α and IL-1ß) in the colon and also improved the histopathological scores of the colonic region. Taking into consideration the above mentioned facts, it can concluded that the developed ligand appended chitosan– ethyl cellulose microspheres could be used as a promising tool for the treatment of IBD.