New Delivery Pathway to Intestinal Lymphatic System: Bile Acid Transporter-Mediated Nanoparticle Absorption
Zoom link: https://us02web.zoom.us/j/85085747255
Webinar ID: 850 8574 7255
Passcode: 393374
Abstract
Biologics and certain classes of small molecules 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 low and their clinical translation yet remains to be proven.
We are exploring a paradigm-shifting approach for intestinal absorption of intact nanoparticles by combining enterohepatic recycling of bile acids and the fat digestion process. Bile acids are secreted to duodenum from the gallbladder to emulsify fats to help digest and massively recycled from distal ileum to the liver with high efficiency (15-20 g/day/adult with ~90% recycling efficiency), which is named as ‘enterohepatic circulation.’ The recycling is accomplished by the enterocytes in the distal ileum and the hepatocytes, which express a series of specialized bile acid transporters. In the meantime, the digested and absorbed fat molecules in the upper small intestine are re-assembled to triglycerides which form nanoparticles (chylomicron (CM)) along with other biological components in the enterocytes. CM is transported to the intestinal lymphatic system.
Nanoparticles of which surfaces are modified with bile acids are transported, after oral ingestion, to the ileum, bind apical sodium-dependent bile acid transporter (ASBT), and are absorbed by endocytic mechanisms. The absorbed nanoparticles seem to share the transcellular pathway of CM even at the distal ileum. This presentation will share solid evidence supporting new uptake pathways of a prove nanoparticle with a high oral bioavailability as high as 47% and reports a practical platform nanotechnology for oral delivery of select molecules having poor oral bioavailability.
Speaker biography
Dr. You Han Bae is Distinguished Professor in Pharmaceutics at the University of Utah. His expertise includes responsive polymers and their biomedical applications and novel delivery systems for cells, proteins, genes, and small molecules. In these fields, he has published more than 300 research articles/book chapters/patents (Google Scholar: citations > 37,000 with h-index of 96) and been recognized as one of Highly Cited Researchers each year for 2014-2018 (by Thomson Reuters, Clarivate Analyatics) in the field of pharmacology. He is an elected fellow of AIBME, AAPS, and CRS. He is currently interested in oral nanoparticle absorption and drug delivery.