Description
- 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.
- Notes:
- Thesis (Ph. D.)--Brown University, 2022
Citation
Baptista, Cameron,
"Novel Methods in Polymer Drug Delivery"
(2022).
Biomedical Engineering Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://repository.library.brown.edu/studio/item/bdr:fm8g75kh/
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Biomedical Engineering Theses and Dissertations
Theses and Dissertations for the Biomedical Engineering department....