Cortisone-loaded stearoyl ascorbic acid based nanostructured lipid carriers alleviate inflammatory changes in DSS-induced colitis.

Abstract

Ulcerative colitis is a chronic inflammatory disease which poorly affects the colon and spreads toward the rectum over time. Cortisone (CRT) is a corticosteroid clinically used for the management of inflammatory diseases like colitis and other inflammatory bowel diseases. Due to some physicochemical properties' cortisone has limited potency in clinics. To overcome drug-related problems, we successfully prepared lipid nanocarriers with generally regarded as safe (GRAS) materials approved by USFDA. The present study aimed to assess the therapeutic efficacy of CRT-loaded 6-o-stearoyl ascorbic acid (SAA) nanostructured lipid carriers (NLCs) against DSS-induced colitis mice. Formulation and characterizations of reported nanostructured lipid carrier were performed according to our previously optimized parameters. The average hydrodynamic diameter of NLCs was 182nm as measured by DLS with 81.14% encapsulation efficacy. TEM, AFM and SEM images analysis confirmed its spherical appearance. hTERT-BJ cells viability up to a dose of 500μg/ml shows cytocompatible characteristics of blank NLCs. CRT-loaded NLCs treatment normalizes physically observed parameters such as disease activity index, weight variation etc. These NLCs were able to significantly reduce the severity of colitis in terms of colon histoarchitecture, regaining of the goblet cells, mucins secretions, inhibition of proinflammatory cytokines etc. Treatment with CRT-loaded NLCs effectively downregulated the overexpression of inflammatory enzymes like cyclooxygenase-2 (COX-2), Inducible nitric oxide synthase (iNOS) etc. The results of this study concluded that these CRT-encapsulated NLCs efficiently manage the disease severity induced by DSS.