Josh Palacios

BME PhD Thesis Defense

Date: November, 3rd 2020 

Time: 1:00 PM

BlueJeans: https://bluejeans.com/336471157

Committee Members: 

Mark Prausnitz, PhD (Georgia Institute of Technology, School of Chemical and Biomolecular Engineering) (Advisor)

Wilbur Lam, MD, PhD (Georgia Institute of Technology, School of Biomedical Engineering)  

Julie Champion, PhD (Georgia Institute of Technology, School of Chemical and Biomolecular Engineering)  

Todd Sulchek, PhD (Georgia Institute of Technology, School of Biomedical Engineering)  

Andrew Neish, MD (Emory University, School of Medicine)

Title: High velocity delivery of biologics from oral dosage forms to the gastrointestinal tract.

Abstract: Biologics are a class of drugs that are critical in treating numerous chronic diseases that afflict hundreds of millions of patients globally. Generally administered through repeated injections, sometimes throughout a patient’s lifetime, these injections can be painful, and increase patient non-compliance, cost of therapy, and risk of spreading blood borne diseases. Oral delivery is preferred, but there are physiological barriers within the gastrointestinal tract (GIT) that generally reduce bioavailability of biologics to less than 2%. The mucus barrier and the epithelial cell layer are the two main barriers that play a major role in preventing the transport of biologics into systemic delivery, resulting in negligible oral bioavailability.

The objective of this dissertation was to improve the oral bioavailability of biologic therapeutics by using pressure-driven flow to facilitate rapid transport across the mucus and epithelial barriers of the GIT. To accomplish this, I first investigated the use of pressure-driven flow as a potential mode of drug transport across the GIT in pig small intestines ex vivo. Next, I designed and developed oral dosage forms that eject their contents at optimal delivery pressures while in simulated gastrointestinal environments. These delivery systems are made from biocompatible materials and excipients, can carry a variety of biologic therapeutics, and can deliver therapeutic payloads at high velocities in a controlled manner. As a proof of concept, I used these delivery systems to deliver insulin to rat small intestines in vivo. As a result, this mode of delivery significantly increased plasma concentration of insulin and significantly reduced blood glucose levels in rats compared to conventional oral delivery. Compared to subcutaneous injections there was no significant difference. In conclusion, these oral dosage forms could serve as an alternative oral delivery platform to injections that are painless, can carry a variety of biologic therapeutics, and can transport biologics rapidly across the GIT barriers, thus increasing systemic delivery.