Organosilica nanoparticles, due to their versatile properties, attract considerable attention for pharmaceutical applications. The first chapter of this thesis gives an introduction to organosilica materials and traditional methods of their synthesis, provides a literature review on functionalisaUon of silica nanoparticles, in particular PEGylation, and describes recently investigated routes of their application in pharmaceutical science. This is followed by a brief description of methods and techniques used in the current study for synthesis and characterisation of organosilica nanoparticles. Chapter 3 represents a novel size-controlled method of synthesis of thiolated and PEGylated organosilica nanoparticles from 3-mercaptopropyltrimethoxysilane (MPTS) using various organic solvents as media. The mechanism of the nanoparticle formation is proposed, the dependence of nanoparticles size on solvent's dielectric constant is determined, and other factors affecting the nanoparticle size are investigated. Thiol-groups on the surface of organosilica nanoparticles are available for a direct conjugation. Therefore, their surfaces were funcUonalised with two types of fluorescent dyes and PEG maleimide of two molecular weights (750and 5000 Oa). Additionally, polymer- and surfactant-templated mechanisms of MPTS nanoparticle formaUon are reported. The synthesis chapter is followed by studying the properties of thiolated and PEGylated organosilica nanoparticles. Mucoadhesive properties of silica nanoparticles were investigated using a newlyintroduced in vitro method assessing their retention ability on the urinary bladder by the means of fluorescence microscopy. The main factors affecting mucoadhesive properties of MPTS nanoparticles were revealed and thiolated nanoparticles were demonstrated to be promising mucoadhesive materials for intravesical drug delivery. PEGylated nanoparticles were found to be less mucoadhesive which led to the hypothesis of providing better permeation by PEGylation. This was considered in the subsequent chapter (chapter 5), studying the barrier functions of the cornea using thiolated and PEGylated nanoparticles. The "whole eye" in vitro method combined with the fluorescence microscopy demonstrated a good permeation of the latter through de-epithelialised ocular tissue into the stroma. This revealed the interaction of nanoparticles with the corneal surface to be a more impcrtant factor than the particle size, determining their permeation ability. As most organs of the human body are covered with biological hydrogels, the ability of silica nanoparticles to permeate through biological tissues has risen an interest in studying their capability to diffuse through such gels. Therefore, the diffusion of thiolated and PEGylated nanoparticles in different polymer solutions, which were selected as prototypes of biological hydrogels, was studied using NanoSight tracking analysis with fluorescent detection. The main factors affecting the diffusion of organosilica nanoparticles were revealed, and it was demonstrated that the presence of strong attractive interactions between the nanoparticles and macromolecules present in solutions can hamper the diffusion. This was followed by studying biocompatible properties of organosilica nanoparticles using an alternative to traditional methods, a slug mucosal irritation test, revealing their non-irritant nature. Finally, the general results of the current study are summarised and discussed in the last chapter of the thesis, proposing plans for the future work and expansion of the investigations on organosilica nanoparticles presented so far.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:659018 |
| Date | January 2014 |
| Creators | Mun, Ellina A. |
| Publisher | University of Reading |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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