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University of Wisconsin-Madison

Pharm Sci Seminar – You Han Bae, PhD

May

11,

2018

You Han Bae, PhD
Professor, Pharmaceutical Chemistry
University of Utah College of Pharmacy

Host: Seungpyo Hong

A Simple Platform Nanotechnology That enables to Convert Injectable to Oral

Bile acids (BA) are biological surfactants synthesized in the liver and secreted to the duodenum via the gall bladder to help digest dietary fats. Enterohepatic circulation recycles BA between distal ileum and liver with a capacity of ~ 12-18 g/day in humans.  Absorptive enterocytes in the distal ileum (ileocyte) and hepatocytes are responsible for the recycling and equipped with a series of transporters operating with efficiencies as high as 90%. A forefront transporter, apical sodium-dependent BA transporter (ASBT), is a molecular pump that transforms to a receptor upon contacting soluble macromolecules decorated with BA.  Digested fat molecules are absorbed into enterocytes and re-assembled back to fat molecules that are released from enterocytes in a nanoparticle form, along with lipoproteins and cholesterol, and processed by endoplasmic reticulum and Golgi body. Resulting fatty nanoparticles (chylomicrons) are transported to systemic circulation via the lymphatic system (i.e., thoracic duct) and the left subclavian vein. We propose new pathways for oral nanoparticle absorption from GIT, combining apical bile acid transporter-mediated cellular uptake and chylomicron transport pathways. This strategy has proven remarkably effective for the delivery of experimental probe nanoparticles and prototype pharmaceutical formulations of various active pharmaceutic ingredients (API), covering small molecules, biologics, as well as genetic materials. For an example, average oral bioavailability (BA) is 45% for BA-decorated polymeric (100-nm diameter) with sustained pharmacokinetic profiles in orally dosed fasted rats.  Similar rat BA were observed for oral nanoparticle dosing ranging from 1 to 20 mg/kg. This oral route is unique to directly deliver intact nanoparticles to central lymphatic ducts where immune cells and their secretion products are enriched.

Date
Friday, May 11, 2018
Time
11:00 AM – 12:00 PM
Location

1116 Rennebohm Hall

Madison, WI 53705