NANOPARTICLES AS CARRIERS FOR ORAL PEPTIDE ABSORPTION - STUDIES ON PARTICLE UPTAKE AND FATE

Previous work from our laboratories has provided quantitative proof of the importance of the gut associated lymphoid tissue (GALT) in the processes involved in the uptake of polystyrene nanoparticles delivered orally, and has confirmed the role of the Peyer's patches in the uptake of particles through the small intestine. In more recent work discussed here the role of lymphoid tissue in the large intestine has been demonstrated, a significant amount of the total uptake occurring in this region of the gut. Adsorption of poloxamers 188 and 407 onto 50 nm polystyrene nanoparticles inhibited uptake in the small intestine and reduced uptake from the large intestine, suggesting reduction in adhesion to GALT and other epithelial tissues in the presence of the poloxamer coating but also indirectly suggesting differences in the surface characteristics of lymphoid tissue at different sites in the gut. The covalent attachment of tomato (Lycopersicon esculentum) lectin molecules to the surface of 500 nm polystyrene particles had a significant effect not only on total uptake (well over a IO-fold increase in absorption over 'plain' particles after 5 days daily dosing) but on the locus of uptake, which is shifted from lymphoid to normal non-lymphoid intestinal tissue. We have demonstrated, therefore, both an increase and a decrease in absorption of nanoparticles from the gastro-intestinal tract and some, albeit serendipitous, control of the site of uptake and absorption, which should provide pointers for the future development of systems with optimal uptake characteristics.