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.

Research advancements and perspectives of inflammatory bowel disease: A comprehensive review

“…For example, budesonide-loaded nanosized micelles and Cortisone-loaded 6-o-stearoyl ascorbic acid nanostructured lipid carriers effectively attenuate DSS-induced colitis. 161 , 162 DSS-coated hollow mesoporous manganese dioxide NPs as carriers to deliver budesonide, reduce the side effects of budesonide and improve the anti-inflammatory effect. 163 Polymer polyethyleneimine (PEI) mucoadhesive NPs loading dexamethasone derivatives (DDs) could enhance DDs enrichment and retention in the colitis site.…”

Orally Administered Silicon Hydrogen Nanomaterials as Target Therapy to Treat Intestinal Diseases

“…isfactory stability of SiH NPs in SGF/SIF inspired us to further investigate their potential in preventing IBD via oral administration. C57BL/6 mice were administered 3% DSS solution in drinking water for 5 days to induce an IBD model according to the standard protocol 7,38,39 (Figure 4A). 5-Aminosalicylic acid (5-ASA), a commonly used drug to treat mild-to-moderate ulcerative colitis in a clinical setting, 40 was used as the positive control.…”

Conjugation, Prodrug, and Co-Administration Strategies in Support of Nanotechnologies to Improve the Therapeutic Efficacy of Phytochemicals in the Central Nervous System

“…Mishra and co-authors developed budesonide (BUD)-loaded micelles for the management of ulcerative colitis (UC) in a mouse model [ 90 ]. UC is an inflammatory bowel disease (IBD) causing chronic inflammation in a specific portion of the large intestine.…”