Poly-conjugated oligomers (p-COs) for noninvasive functional protein delivery

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PART 1: NON-TECHNICAL SUMMARYProtein-based drugs have shown great promise and high impact in managing and treating many diseases owing to their higher safety profile than conventional small drugs. Unfortunately, the current administration of those protein-based drugs is largely limited to painful invasive injections to achieve therapeutic concentrations in the blood. Such administration methods are painful to the patient and require specialized personnel, which are an obvious burden for more widespread disease management and treatments. This fundamental issue is due to the instability and large sizes of proteins. This project will ultimately introduce novel protein delivery materials that address the major biological hurdles that currently block more patient-friendly uses of protein-based drugs. In this short project, the feasibility of protein transporting efficiency of a biomaterial will be established using a well-accepted cell model system. PART 2: TECHNICAL SUMMARYDespite the high clinical success of therapeutic biologics, the current administration of therapeutic proteins heavily relies on invasive injections due to cell impermeability and instability of biologics. Patient-friendly noninvasive oral, nasal, or inhalation routes are largely limited by poor mucus diffusion and transepithelial transport. The ultimate goal of this project is to develop a conceptually new conjugated oligomer (CO)-based degradable polymer (p-CO) that can be used for the noninvasive delivery of therapeutic proteins. The proposed biomaterials must exhibit stable complexation with proteins, efficient mucus diffusion, and efficient epithelium entry followed by transepithelial transport to the blood. In this short project, the transepithelial transport efficiency of model p-CO/fluorescent protein complexes will be assessed by monitoring the fluorescent intensity of proteins in the basolateral compartment of the transwell covered with a mucus expressing epithelium cell monolayer. The successful completion of this project would strengthen the feasibility of using p-COs for future noninvasive protein delivery. Ultimately, the proposed system would have a high transformative potential and broader impact on noninvasive (e.g., oral, nasal, or inhalation) delivery of biologics to treat or manage various disease or vaccine development.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.