Author ORCID Identifier
0009-0007-5467-2725
Document Type
Dissertation
Date of Award
5-31-2026
Degree Name
Doctor of Philosophy in Chemical Engineering - (Ph.D.)
Department
Chemical and Materials Engineering
First Advisor
Kathleen McEnnis
Second Advisor
S. Basuray
Third Advisor
Richard T. Cimino
Fourth Advisor
Murat Guvendiren
Fifth Advisor
Jonathan M. Grasman
Abstract
The glass transition temperature (Tg) of poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles plays a crucial role in governing molecular mobility, diffusion, and consequently, drug release kinetics. However, the interaction among residual surfactant, drug effect, nanoscale confinement, and release medium on Tg remains insufficiently characterized. This study aims to bridge this gap by correlating the thermal behavior of PLGA nanoparticles with their drug release behavior under physiologically relevant conditions.
In the present study, PLGA nanoparticles were synthesized using both nano-emulsion and surfactant-free nano-precipitation approaches. The influence of residual surfactants - poly(vinyl alcohol) (PVA) and didodecyldimethylammonium bromide (DMAB) - was systematically investigated to decouple interfacial plasticization from confinement effects. The incorporation of a hydrophobic model drug, flurbiprofen, was employed to probe drug-induced plasticization and to establish quantitative relationships between drug loading and Tg depression. The resulting nanoparticles, ranging from 80 to 250 nm, were characterized by temperature modulated differential scanning calorimetry (mDSC), nanoparticle tracking analysis (NTA), and 1H NMR to determine glass transition temperature, size distribution, and surfactant content, respectively. Tg measurements were further performed in various media including phosphate-buffered saline (PBS) and protein-containing solutions to assess hydration- and protein corona-induced mobility.
Results demonstrate that residual surfactants and flurbiprofen loading both significantly affected Tg through blending and plasticization. Exposure to aqueous and protein environments further depressed Tg by 10-15 °C, due to water plasticization and the presence of a protein corona. Importantly, the observed Tg variations directly translated to differences in release behavior: nanoparticles with lower Tg values displayed accelerated diffusion release, while those with higher Tg maintained prolonged, diffusion-controlled release profiles.
Overall, this study establishes a mechanistic framework linking thermal property to macroscopic drug release kinetics in PLGA nanoparticles. By isolating the effects of surfactant, drug incorporation, confinement, and release environment, the findings highlight Tg as a predictive parameter for rational design and tuning of biodegradable nanocarriers in controlled drug delivery applications.
Recommended Citation
Liu, Guangliang, "Glass transition temperature of PLGA nanoparticles and the application in drug delivery" (2026). Dissertations. 1883.
https://digitalcommons.njit.edu/dissertations/1883
