High Velocity Delivery of Biologics from Self-Pressurized Oral Capsules to the Gastrointestinal Tract
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Palacios, Joshua
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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 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 gastrointestinal tract. To accomplish this, we first investigated the use of pressure-driven flow as a potential mode of drug transport across the gastrointestinal tract in pig small intestines ex vivo. Next, oral dosage forms that eject their contents at optimal delivery pressures while in simulated gastrointestinal environments were engineered. These delivery systems were made from biocompatible materials and excipients, can carry a variety of therapeutics, and can deliver therapeutic payloads at high velocities in a controlled manner. As a proof of concept, these delivery systems were used 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 comparable to subcutaneous injections. In conclusion, these oral dosage forms could serve as an alternative oral delivery platform to injections that are painless, can carry a variety of therapeutics including biologics, and can transport these therapeutics rapidly across the gastrointestinal barriers, thus increasing systemic delivery.
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Date
2021-05-01
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Dissertation