Sufeng Zhang, PhD
Instructor in Medicine
Sufeng Zhang, Amy T. Jin, Samson Afewerki, Wen Tang, Rachel Y. Zhang, Lihong Jing, Yixuan Zhou, Heng Zhang, Jochen K. Lennerz, Joshua R. Korzenik, Giovanni Traverso
Research Category: Allergy, Immunology, Inflammation, and Infectious Diseases
Targeting the site of inflammation represents an ideal approach for treatment of inflammatory bowel disease (IBD). Negatively charged drug carriers have been shown to preferentially adhere to the inflamed mucosa, facilitating drug delivery targeting inflammation in IBD. Here, we report modulation of charges on thermo-responsive poly(N-isopropylacrylamide)-based polymers and comparison of the resultant polymers’ gelation and adhesion to inflamed colon in experimental colitis in mice. We showed that both the types of chemical modification and polymer molecular weight affected the adhesion of resultant hydrogels to the inflamed colon. We further quantified disease parameters in experimental colitis for individual mice and correlated with polymers’ adhesion. Our study suggests a new strategy for targeting the inflamed colon through harnessing charge-mediated interaction and thermo-responsiveness of PNIPAM-based polymers. The examination of their mucosal binding provides further understanding of interactions between polymeric hydrogels and the biological interface in colitis.
A major hurdle in treatment of ulcerative colitis (UC) is the lack of effective drug carriers that can precisely deliver the required amount of drug to the inflamed colon. Available therapies are with severe side effects, largely because they are not only absorbed at the diseased tissue but also being absorbed by the healthy tissue when directly administered by patients. We focus on developing formulations that can provide improved local drug administration in UC treatment. This new formulation utilizes a “smart” material that is responsive to temperature change. We also design the material so that it has strong affinity towards ulcers. Therefore, when administered, it is a liquid for broad dispersion in the colon; after contacting the colon, the liquid gels and forms “drug depots” at the ulcers. This helps to maintain the drug locally at the active sites of ulcers where it is needed while minimizing the adverse effects of drugs at the healthy tissue. These studies were performed in preclinical models of UC that develop similar colitis to human UC, as a prerequisite for future studies.