Inflammatory bowel diseases (IBDs) including Crohn’s disease (CD) and ulcerative colitis (UC) are characterized by an inappropriate immune response in a genetically susceptible host. Despite a variety of therapeutic options including anti-inflammatory, immunosuppressive, and biologics, up to 20% of UC patients and more than 50% of CD patients eventually require surgery. There is an unmet need for a transformative therapeutic strategy for this disease. One of the major roadblocks for effective IBD intervention is the lack of a system for robust and targeted delivery of drugs specifically to the site of inflamed intestinal tissues. Nanoparticles (NPs) can target inflamed tissues, therefore, have advantages over conventional micronized drug formulations. Two main delivery systems have demonstrated the efficacy of targeting inflamed intestine. Muco-penetrating particles (MPPs), which possess dense poly(ethylene glycol) (PEG) brushes, can diffuse through mucus layers, and are deeply retained in mucosal layers. Muco-adhesive particles (MAPs), on the other hand, have charged surface and anchor to the adherent mucus on luminal surface. However, previous investigations on the interaction between NPs and host tissues were macroscopic and/or non-quantitative. Moreover, the interaction of NPs with luminal contents, such as the luminal microbiota and mucus, was overlooked. Herein, we systemically investigated the distribution of NPs in inflamed colons as a function of NP surface chemistry. Negatively charged MAPs, (N-MAPs), MPPs and positively charged MAPs (P-MAPs) were synthesized with FDA approved excipients and rectally administered in a murine colitis model. To enable the microscopic visualization and quantification of differentially charged NP distribution throughout the colons, we developed a whole colon scanning method(Figure). Our analysis demonstrates, for the first time, how the surface chemistry affects the association of NPs with luminal contents as well as host tissues throughout the whole colon.

Interactions of differentially charged nanoparticles with bacterias, mucus, and host tissues

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.