Development and Optimization of Ligand Appended Nano-Structured Lipid Carrier System for the Treatment of Inflammatory Bowel Disease

Abstract

Inflammatory bowel disease is a cascade of inflammatory conditions marked by aberrations in small intestine and colon. It is a long lasting disease and the treatment includes long term doses that causes severe adverse effects as a result of systemic absorption. Hence a local targeted treatment that aids delivering the drug at the site of inflammation serves as a safe therapy. Budesonide is a gluco corticoid that inhibits various inflammatory cells causing induction in remission of active disease. The present study deals with formulation of a targeted preparation of budesonide loaded nano-structured lipid carriers (NLCs) that helps local delivery of drug without getting degraded in body. The NLCs were designed by using combination of a solid lipid Compritol ATO 888 and a liquid lipid Labrafac WL 1349, a medium chain triglyceride (MCT). The main advantage of using a MCT was that it itself serves an inhibitory effect in intestinal inflammation by inhibition of TNF-α and Interleukins and thereby enhancing the healing activity of the formulation. NLCs were prepared by using hot omogenization technique. Various preliminary trials were performed for optimization of the NLCs in which process as well as formulation parameters were studied. Based on preliminary trials, 3 factors viz. concentration of drug, concentration of surfactant and concentration of co-surfactant were optimized using Box-Behnken Design. The lyophilized NLCs were converted to pellets by using simple extruder-spheronizer and were enteric coated in order to protect the pellets from degradation in upper part of gastro-intestinal tract. Characterization of the formulation and in-vivo studies were performed on colitis-model to ensure the efficacy of the prepared formulation and parameters such as myeloperoxidase activity, determination of inflammatory markers and histopathology was studied.