Development of P(TMC)-Based Polymers for Sustained Delivery of Acid-Sensitive Drugs
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Authors
McNutt, Josiah
Date
Type
thesis
Language
eng
Keyword
octreotide , drug delivery , trimethylene carbonate , peptide , acid-sensitive , sustained release , PTMC
Alternative Title
Abstract
Peptides are a quickly growing drug class, which continue to garner attention in pharmaceutical research due to their applications in the treatment of a variety of diseases. The major challenge when working with these drugs is their rapid degradation in vivo and poor membrane-permeability. This makes simple administration via oral routes infeasible and necessitates the use of a localized drug delivery system. One example of such a system is to load the peptide into a biodegradable polymer which is then injected close to the drug’s site of action. The polymer provides extended drug release, before degrading and being removed by the body. This is done commercially by a polymer called poly(lactide-co-glycolide), or PLG. However, PLG breaks down to form highly acidic by-products, which react with the peptide and alter the drug’s chemistry. Depending on the peptide, this can lead to reduced effectiveness or inactivation. In this work, a P(TMC)-based polymer was synthesized and assessed as a delivery vehicle for acid-sensitive drugs. P(TMC-HTMC-BtTMC) copolymers with varying compositions and molecular weights were examined. Ultimately, a low molecular weight viscous liquid formulation was the most feasible delivery option, and its degradation was characterized. Release of a representative peptide drug, octreotide, from the polymer was also studied. Increasing the HTMC content resulted in increased degradation, but complete degradation of the polymers was not achieved after 8 weeks, with degradation slowing considerably as HTMC content approached 15%. Modification of the octreotide was reduced in comparison to studies done using PLG.
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ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.