Functionalized Zirconium Phosphate Nano Platelets - From Surface Design to Drug Delivery

Abstract

The chemical characterization of nanomaterials in the realm of drug delivery and surface modification is on the current frontiers of analytical chemistry. A drug delivery vehicle must be able to carry therapeutic cargo and be able to reach the intended target or compartment. This dissertation will focus on the analytical characterization of zirconium phosphate (ZrP) in both alpha and theta phases as a drug delivery matrix utilizing multiple unique and novel analytical techniques.

In the first area we present for the first time, a methodology for the characterization of individual drug loaded 150 nm ZrP nanoparticles (NPs) by obtaining molecular information from single massive cluster impacts. The clusters used in this secondary ion mass spectrometry (SIMS) technique are Au_(400)^(4+) and C_(60)^(+/2+). The ionized ejecta from each impact are recorded individually which identifies ions emitted from a surface volume of ~10 nm in diameter and 5-10 nm in depth. The mode of analyzing ejecta individually from each single cluster impact gives insight into chemical homogeneity within nanodomains.

The in vitro biological release profile was investigated in simulated biological environment for the drug-ZrP nanocomposites. The release profiles reveal a direct dependency with the pH of the medium for the release of the complexes indicating targeting opportunities. Additionally the NP matrix breaks down in the artificial lysosomal fluid medium at pH – 4.5 indicating good bio-clearance possibilities, a major issue that plagues several alternative drug delivery carriers. This project is expected to give rise to a facile drug delivery matrix that is highly biocompatible and leads to greater targeted gentoxicity for cancerous cells.

The second area of research presented in this dissertation investigates the surface modification of 150 nm α-ZrP NPs utilizing a host of different organo modifiers. α-ZrP was surface modified by reacting surface P-OH groups with 3-(triethoxysilyl)propyl isocyanate(TEPI), dichloromethyl(phenyl)silane(DCMPS) and lauryl methacrylate(LMA). SIMS in the event-by-event bombardment detection mode was utilized to calculate the degree of surface coverage for a brand new platform in conjunction with TGA, FTIR and XRPD to detail the surface confinement of the molecular assemblies. New discoveries continue to be made by creative scientists’ everyday pushing what we know about inorganic layered materials and the analytical chemistry that drives this field.