Excellence in Research: Novel Polysaccharides for Cell-Specific Delivery

NON-TECHNICAL SUMMARY: Taking medicines by mouth is the most common and preferred way to deliver drugs because it is easy, painless, and convenient for patients. However, after a medicine is swallowed, it must travel through the digestive system, which comprises of different organs such as the stomach, small intestine, and large intestine. These different organs have different barriers that can stop the drug from reaching the right place or being absorbed in the blood effectively. Polymers are long molecules that have been used to help drugs overcome these barriers. These polymers can be designed to release drugs at the right time, carry them to the right locations, and improve how effectively the human body absorbs them. This project will advance national priorities in Biotechnology by studying how polymer structure affects oral delivery to make medicines more effective. Along with this research, the project will start a professional development workshop for Howard University’s undergraduate and graduate students where the students interact one-on-one and network with scientists working in the industries and academic research labs to enhance career readiness, foster research excellence, and workforce development. TECHNICAL SUMMARY: Oral administration remains the preferred route for drug delivery due to its noninvasive nature, convenience, and strong patient adherence. However, the gastrointestinal (GI) tract presents a series of dynamic physiological barriers that limit the bioavailability and site-specific delivery of many therapeutics. Polymers serve as the primary materials platform for overcoming these challenges, enabling pharmaceutical scientists to engineer formulations with controlled release, targeted transport, and enhanced absorption. However, these conventional polymers primarily focus on linear polymers, overlooking the potential of non-linear architecture and ligand density. Along with this, the majority of these polymers generate acidic microenvironments during degradation resulting in localized acidification that can destabilize pH-sensitive therapeutic agents and impair absorption. This proposal harnesses the branched architecture of ethoxy acetalated dextran (Ace-DEX), which enables systematic control over ligand density. By precisely tuning ligand density, accessibility and optimizing non-linear Ace-DEX architecture, this study aims to establish predictive structure–property relationships that inform the rational design of next-generation biomaterials for enhancing the therapeutic efficacy, while deepening our understanding of how molecular architecture governs polymer–biological interactions in oral drug delivery. The education and outreach activities include collaborating with scientists working in the industry and academic research labs, field trips, and career guidance for Howard University’s undergraduate and graduate students through professional development workshops. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.