Abstract

New Oral Absorption Pathway of Nanoparticle

You Han Bae, Distinguished Professor, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah

All nanomedicine assumes injection for administration. Biologics show extremely poor oral bioavailability due primarily to limited solubility, low permeability and digestive enzymes. Clinical trials of various small-sized peptides (not larger than insulin) with permeation enhancers and enzyme inhibitors have documented only limited oral bioavailability. If protective nanoparticles loaded with such active ingredients were absorbed from the gastrointestinal tract, it would overcome most of issues relevant to poor bioavailability. Various approaches for nanoparticle oral delivery, based on receptor-mediated endocytosis and M-cell uptake, have been explored, the uptake rates have, however, been limited and their clinical translation yet remains to be proven.

We are exploring paradigm-shifting approaches for intestinal absorption of intact nanoparticles by combining fat digestion processes and enterohepatic recycling of bile acids.

Nanoparticles of which surfaces are modified with bile acids are transported, after oral administration, to the ileum, bind apical sodium-dependent bile acid transporter (ASBT), and are absorbed by unknown endocytic pathways. The nanoparticles then seem to share the transport pathway of chylomicron. This presentation will demonstrate solid evidences supporting a new nanoparticle uptake pathway, report a platform nanotechnology for oral drug delivery, and summarize high oral bioavailability of selected small molecules, peptides/proteins and nucleic acids at a reasonable dose range to meet corresponding therapeutic windows in rodent models.