(214g) Novel Biodegradable Drug Carriers for Oral Protein Delivery
AIChE Annual Meeting
Tuesday, November 18, 2008 - 10:40am to 11:00am
Despite advancements in the synthesis of protein therapeutics, the standard administration method has remained by injection. This delivery route has frequently resulted in poor patient compliance, especially among children. Considerable effort has thus been placed on developing alternative and non-invasive delivery routes, in particular through oral administration. Though the oral route is regarded as the most convenient and practical administration route, two major obstacles limit its viability: enzymatic degradation in the gastrointestinal tract (GI) and physical transport across the epithelial layer into systemic circulation. These barriers limit the bioavailability of most proteins to well below 1%.
The proposed delivery mechanism involves encapsulating proteins within a biodegradable polymer shell, which protects proteins from enzyme digestion. To increase physical uptake across the epithelial layer, the polymer vehicle will be conjugated to transferrin (Tf), an active carrier protein involved in iron transport. Transferrin is highly expressed in the GI tract, and thus been investigated as an active carrier for orally delivered drugs. The nanoparticle-Tf conjugate will take advantage of a receptor-mediated transport pathway that actively transports the drug carrier across the cell rather than relying on passive diffusion. These polymer carrier-Tf conjugates have been shown to increase uptake by up to 400% in tumor cells, where Tf-receptors are also high expressed.
The focus of this research will be effect of particle size on the degree of transport across the epithelial layer. Though past research has shown that smaller particles are more easily transported than larger ones, this study will attempt a more statistical approach to determine a correlation between size and uptake. Particles will be analyzed using dynamic light scattering (DLS) and a scanning electron microscope (SEM).