Date of Award

Spring 2019

Document Type

Thesis

Degree Name

Master of Science in Chemical Engineering - (M.S.)

Department

Chemical and Materials Engineering

First Advisor

McEnnis, Kathleen

Second Advisor

Guvendiren, Murat

Third Advisor

Xu, Xiaoyang

Abstract

Drug delivery plays an important role in targeted therapies and nanoparticles which can be used as drug carriers and it’s a frequently researched topic. Poly(lactic-co-glycolic acid) (PLGA), a highly biocompatible polymer, has been used as a drug delivery vehicle in many studies. One of the challenges facing drug delivery particles is the problem of burst release which is when a large amount of the drug is suddenly released from the particle once it is placed in the body. This is generally undesirable as usually a slow and controlled release is preferred. The glass transition temperature has an effect on drug release behavior like the burst effect. In the case of PLGA, the effect can be pronounced since the glass transition temperature is close to body temperature. The glass transition phenomena of PLGA has been well researched in the past but the effect of thermal history on glass transition temperature of PLGA is yet to be investigated. With the development of temperature modulated differential scanning calorimetry (DSC), however, the glass transition temperature can be well separated from the effects of polymer aging commonly seen overlapping the glass transition in the DSC scan on initial heating of polymer samples. Thus, temperature modulated DSC provides the possibility to study the effect of thermal history on glass transition temperature.

To accurately study the effects of thermal history on the glass transition temperature of PLGA particles, particles need to be made of the same size, using the same PLGA, by different methods. In this study, nanoprecipitation, nanoemulsion and electrospray jetting techniques are used to produce the PLGA nanoparticles. The size is optimized for all three methods to provide the stable production of nanoparticles with similar size distributions. The size optimization includes determination of factors such as the optimal surfactant concentration, optimal polymer concentration, and optimal sonication time. Several sets of nanoparticles made from nanoprecipitation and nanoemulsion are tested using temperature modulated differential scanning calorimetry (TMDSC). Results show that a clear glass transition temperature can be measured on the first heating scan. From these preliminary samples, it appears as though nanoemulsion particles would be preferable over nanoprecipitation particles for drug delivery because for nanoemulsion samples the glass transition temperature is higher and closer to the bulk value and the transition happens over a smaller temperature range. This suggests that particles made by nanoemulsion would have less burst release than particles made by nanoprecipitation.

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