Drug-Loaded Carrier Particles for Improved Oral Delivery for Colon Cancer Prevention

Fast-Track proposals will be accepted. Direct-to-Phase II proposals will be accepted. Number of anticipated awards: 2-4 Budget (total costs, per award): Phase I: up to $400,000 for up to 12 months Phase II: up to $2,250,000 for up to 2 years PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED. Summary Patients with inflammatory bowel disease (IBD), such as ulcerative colitis (UC) and Crohn's disease, are at an increased risk of colorectal cancer (CRC). Existing IBD treatments do not achieve long-term remission in the majority of the estimated 3.1 million IBD patients. The risk of CRC in these individuals therefore progressively increases throughout their lifetime. The cumulative risk of UC-associated CRC was 2%, 8%, and 18% after 10, 20, and 30 years, respectively. Thus, cancer prevention is the key to achieving better health outcomes for these high-risk individuals. CRC prevention in IBD patients requires not only the development of safe and efficacious agents, but also a safe and effective drug delivery system targeting the cancer-predisposed colon. Emerging evidence indicates that carrier particles (e.g., microspheres, nanoparticles) can address limitations of conventional oral drug delivery platforms by allowing agents to pass through biological barriers without degradation and providing sustained release of agents in the colon with improved bioavailability and reduced systemic toxicity. Some examples of agents being developed as carrier particle formulations targeting colon include mesalazine, 5-fluorouracil, progesterone, curcumin, and hydrocortisone. However, there remain challenges including confirmation of efficacy of the agent-loaded carrier particles in relevant animal IBD models and optimization of formulations to improve encapsulation efficiency, sustained release, controlled release, reproducibility, and mass production of dosage forms. The successful development and commercialization of carrier particles for drug delivery to the colon could be transformative for IBD patients and lead to better survival rates, improved quality of life, and increased treatment adherence.