Caffeic Acid-Conjugated Budesonide-Loaded Nanomicelle Attenuates Inflammation in Experimental Colitis.

Abstract

Ulcerative colitis is a multifactorial disease of the gastrointestinal tract which is caused due to chronic inflammation in the colon; it usually starts from the lower end of the colon and may spread to other portions of the large intestine, if left unmanaged. Budesonide (BUD) is a synthetically available second-generation corticosteroidal drug with potent local anti-inflammatory activity. The pharmacokinetic properties, such as extensive first-pass metabolism and quite limited bioavailability, reduce its therapeutic efficacy. To overcome the limitations, nanosized micelles were developed in this study by conjugating stearic acid with caffeic acid to make an amphiphilic compound. The aim of the present study was to evaluate the pharmacological potential of BUD-loaded micelles in a mouse model of dextran sulfate sodium-induced colitis. Micelles were formulated by the solvent evaporation method, and their physicochemical characterizations show their spherical shape under microscopic techniques like atomic force microscopy, transmission electron microscopy, and scanning electron microscopy. The in vitro release experiment shows sustained release behavior in physiological media. These micelles show cytocompatible behavior against hTERT-BJ cells up to 500 μg/mL dose, evidenced by more than 85% viable cells. BUD-loaded micelles successfully normalized the disease activity index and physical observation of colon length. The treatment with BUD-loaded micelles alleviates the colitis severity as analyzed in histopathology and efficiently, overcoming the disease severity via downregulation of various related cytokines (MPO, NO, and TNF-α) and inflammatory enzymes such as COX-2 and iNOS. Results of the study suggest that BUD-loaded nano-sized micelles effectively attenuate the disease conditions in colitis.