Title Information
Title
Novel Methods in Polymer Drug Delivery
Type of Resource (primo)
dissertations
Name: Personal
Name Part
Baptista, Cameron
Role
Role Term: Text
creator
Name: Personal
Name Part
Mathiowitz, Edith
Role
Role Term: Text
Advisor
Name: Personal
Name Part
Darling, Eric
Role
Role Term: Text
Reader
Name: Personal
Name Part
Tripathi, Anubav
Role
Role Term: Text
Reader
Name: Personal
Name Part
Srivastava, Vikas
Role
Role Term: Text
Reader
Name: Corporate
Name Part
Brown University. Biology and Medicine: Biomedical Engineering
Role
Role Term: Text
sponsor
Origin Information
Copyright Date
2022
Physical Description
Extent
17, 244 p.
digitalOrigin
born digital
Note: thesis
Thesis (Ph. D.)--Brown University, 2022
Genre (aat)
theses
Abstract
The ability to encapsulate drugs in a polymer delivery vehicle can have significant practical benefits. Polymers may allow for greater apparent solubility, as well as increased stability of encapsulated drugs. The encapsulation of therapeutic agents in polymer delivery vehicles may also allow for more efficient and effective treatments by providing controlled release of drugs. In the work presented here, we aim to understand select biodegradable polymer behavior and morphology as a function of processing and manufacturing conditions with the ultimate goal of improving their performance as drug delivery vehicles. The focal points of this thesis work reside in two independent projects, which both fall under the broad umbrella of polymeric drug delivery: In Project 1, long acting polymeric delivery depots containing small molecule drugs are explored. The overarching goal of this work was to induce mesomorphic phases into non-mesogenic biodegradable polymers, Poly-l-lactic acid (PLA) and Polycaprolactone (PCL), for the application of long-acting implants to deliver small molecule hydrophobic drugs. Herein, we demonstrate a novel hydraulic compression processing approach to induce mesophase formation in both PLA and PCL. Release experiments conducted on PCL tablets loaded with a model small molecules drugs, dexamethasone, suggest that these processing induced mesophases may serve as a novel method for controlling the rate of drug diffusion. This change in diffusion behavior may be explained by the free volume associated with the induced mesophase morphology In Project 2, polymeric nanoparticle containing biologic drugs are explored. The overarching goal of this project was to understand the impact of solvent and non-solvent choice in the process of Phase Inversion Nanoencapsulation (PIN) to help optimize and develop a poly (lactic-co-glycolic acid) (PLGA) nanoparticle formulation containing a novel glucagon-like peptide-1 receptor agonist (GLP-1 RA) for its long acting oral delivery in the treatment of type 2 diabetes (T2D). Herein, we demonstrate a correlation between the Gibbs energy of mixing between solvent and non-solvent and the resulting particle size, release profile, and encapsulation efficiency. This correlation may be explained though the mechanism of particle formation by supersaturation, nucleation, and growth upon adding a solubilized polymer or drug solution to a miscible non-solvent. Ultimately this correlation between Gibbs energy and particle formation provides a novel approach for the optimization of GLP-1 RA loaded PLGA nanoparticle formulations.
Subject (fast) (authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/01070588")
Topic
Polymers
Subject
Topic
Polymer Films
Subject (fast) (authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/00898667")
Topic
Drug delivery systems
Subject (fast) (authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/01070574")
Topic
Polymeric drug delivery systems
Subject
Topic
Oral Drug Delivery
Subject
Topic
Polymeric nanoparticles
Subject (fast) (authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/00832586")
Topic
Biomedical materials
Subject
Topic
Drug delivery vehicles
Subject (fast) (authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/00898781")
Topic
Drugs--Coatings
Language
Language Term (ISO639-2B)
English
Record Information
Record Content Source (marcorg)
RPB
Record Creation Date (encoding="iso8601")
20220706