Nanomedicine for therapeutic drug therapy: Approaches to increase the efficacy of drug therapy with nanoemulsion delivery and reduce the toxicity of quantum dots.

摘要

The advancement of nanotechnology has paved the way for novel nanoscale materials for use in a wide range of applications. The use of these nanomaterials in biomedicine facilitates the improvement of existing technologies for disease prevention and treatment through diagnostics, tumor detection, drug delivery, medical imaging and vaccine development. Nanotechnology delivery systems for therapeutic uses includes the formulation of nanoparticles in emulsions. These novel delivery systems can improve drug efficacy by their ability to enhance bioavailability, minimize drug side effects, decrease drug toxicity, provide targeted site delivery and increase circulation of the drug in the blood. Additionally, these delivery systems also improve the drug stability and encapsulation efficiency.;In the Introduction, this thesis will describe a novel technique for the preparation of nanoemulsions which was utilized in drug delivery and diagnostic applications. This novel Phase Inversion Temperature (PIT) method is a solvent and polymer-free and low energy requiring emulsification method, typically utilizing oils stabilized by nonionic surfactants to prepare water in oil (W/O) emulsions. The correlation between the particle size, zeta potential and the emulsion stability is described. The use of this nanoemulsion delivery system for pharmaceuticals and nutraceuticals by utilizing in vitro systems was investigated.;Using the PIT method, a self assembling nanoemulsion (SANE) of gamma Tocotrienols (gammaT3), a component of Vitamin E family has been demonstrated to reduce cholesterol accumulation in HepG-2 cells. The nanoemulsion is stable and the particle size is around 20 nm with a polydispersity index (PDI) of 0.065. The effect of the nano gammaT3 on the metabolism of cholesterol, HMG-CoA activity and Apo-B levels were evaluated in an in vitro system utilizing HepG2 cells.;A new class of nanoparticles, Quantum dots (QDs) has shown immense potential as novel nanomaterials used as fluorescent labels. They have been studied extensively due to their interesting optical and electrical properties. The study of their applications has led to their use as novel platforms for delivery into living systems for use in medical imaging. The second part of this thesis discusses the toxicity of the various semiconductor nanocrystals, CdSe and InP. The results show the toxicity of CdSe and InP QDs in in vitro cultures of whole skin biopsies exposed to similar concentrations. This forms the basis for further studies involving QDs and approaches to reduce the toxicity of these nanoparticles.;Finally, ligand exchange mediated Solutol HS-15 modified CdSe QDs were prepared for the first time. The modified CdSe QDs demonstrated long term stability and reduced cytotoxicity. Such behavior is interpreted as arising from decreased aggregation of the QDs due to the incorporation of the surfactant.