NANOPARTICLES FOR MEDICAL IMAGING AND ORAL THERAPEUTICS: FORMULATION DESIGN AND PROCESS IMPROVEMENTS

Abstract

This thesis details the advancements in harnessing flash nanoprecipitation (FNP) technology for therapeutic and diagnostic applications in biology and medicine. FNP nanoparticles can encapsulate a variety of hydrophobic and hydrophilic molecules at high core loadings. This has significant advantages for both medical imaging and drug delivery applications. For example, densely clustered contrast agents improve imaging sensitivity to allow for earlier detection of cancers and other diseases. Nanoparticles also increase the surface area to volume ratio of therapeutic drugs to increase oral bioavailabilities. While FNP in its current form has shown promise in a wide variety of applications, this thesis also describes methods to improve the FNP process and enable even higher loading nanoparticles. This dissertation can be segmented into three different projects. First, we designed copper chelating nanoparticles as contrast agents for positron emission tomography (PET). In a collaborative study with researchers from the University of Pennsylvania, these PET-active nanoparticles demonstrated strong tumor uptake and enabled further animal biodistribution studies. Second, we developed FNP formulations to encapsulate the malaria drug, lumefantrine, to improve its drug dissolution and shelf-life. This thesis focuses on the challenges and approaches during the scale-up process of such a formulation. Lastly, we introduced a novel extension of the FNP process. Sequential FNP (sFNP), which separates the aggregation and stabilization steps of traditional FNP, allows for even high core loadings nanoparticles at smaller sizes. We hope that the work outlined in this dissertation will motivate future studies into expanding FNP nanoparticle technology for medical applications.