Thermo-Responsive Polymers Targeting Inflammation in Murine Colitis

Abstract

Targeting the site of inflammation is an ideal approach for treating inflammatory bowel disease (IBD). Inflammation targeting enables maximal drug-on-target effects while minimizing off-target side effects. Negatively charged drug carriers have been shown to facilitate drug delivery to inflamed colon mucosa after local administration. To modulate the negative charges and integrate responsiveness to stimuli, here we describe thermo-responsive, inflammation-targeting (TRIT) hydrogels based on functionalized poly(N-isopropylacrylamide-co-methacrylic acid) (PNIPAM-MAA). We show that both chemical modification types and polymer molecular weights affect the resultant microgels adhesion to the inflamed colon in dextran sulfate sodium (DSS)-induced murine colitis in vivo. Further, we quantified the correlations between microgels adhesion and colitis severity for individual mice, demonstrating that the microgels adhesion correlated directly with weight loss percentage in DSS-treated mice. By exploiting charge-mediated interaction and thermo-responsiveness, TRIT hydrogels represent a promising strategy to target inflamed colon mucosa as a drug delivery platform for colonic IBD treatment. TeaserThis study developed thermo-responsive, inflammation-targeting (TRIT) hydrogels that harness charge-mediated interaction and sol-to-gel transition to target inflamed colon mucosa as a new approach for treating inflammatory bowel disease.