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Title: Developing mucoadhesive and mucuspenetrating nanoparticles for drug delivery : silica and chitosan models
Author: M. Ways, Twana Mohammed
ISNI:       0000 0004 7966 807X
Awarding Body: University of Reading
Current Institution: University of Reading
Date of Award: 2019
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Mucosal drug delivery is often limited by the presence of several barriers including mucus, the harsh pH and enzymatic activity on the mucosal surfaces. Nanoparticles have shown some potential to overcome these barriers. The aim of this thesis was to investigative how functionalisation of nanoparticles with non-ionic hydrophilic polymers (polyethylene glycol (PEG), polyhydroxyethyl acrylate (PHEA), poly-2-ethyl-2-oxazoline (POZ) and polyvinyl pyrrolidone (PVP)) affects their physicochemical and mucoadhesive properties, diffusion in mucin solution as well as ability to penetrate into mucosal tissues. Silica and chitosan nanoparticles were chosen. Thiolated silica nanoparticles were functionalised with PEG and POZ and therefore three types of silica nanoparticles were obtained; thiolated, PEGylated and POZylated. After the synthesis, the effect of the pH on the size of the silica nanoparticles was studied. No significant change in the size of PEGylated silica nanoparticles over the pH range of 1.5-9 was observed. A significant increase in the size of thiolated and POZylated silica nanoparticles at pH  ≤ 2 was observed. Fluorescently labelled thiolated, PEGylated and POZylated silica nanoparticles were incubated with freshly excised rat intestinal mucosae. Then, the mucosae with the nanoparticles were washed with phosphate buffer solution for several cycles and their fluorescent images were taken. It was found that PEGylated and POZylated silica nanoparticles were less mucoadhesive compared to the thiolated counterpart. This was evident by the lower fluorescence signal of the PEGylated and POZylated silica nanoparticles compared to the thiolated counterpart. Four chitosan derivatives (PEG-, PHEA-, POZ- and PVP-chitosan) were synthesised, which showed complete solubility over a broad pH range (3-9). Unmodified and modified chitosan nanoparticles were prepared using ionic gelation with sodium tripolyphosphate. Modified chitosan nanoparticles diffused faster in bovine submaxillary mucin solution measured by nanoparticle tracking analysis. The penetration of chitosan nanoparticles was evaluated using fluorescence microscopy and demonstrated that modified chitosan nanoparticles penetrated deeper into sheep nasal mucosa compared to unmodified chitosan nanoparticles. The possibilities of incorporating psychoactive drugs (haloperidol and phenobarbital) into unmodified and PVP-chitosan nanoparticles were investigated. Haloperidol-unmodified chitosan nanoparticles showed a relatively low loading capacity. However, phenobarbitalunmodified and PVP-chitosan nanoparticles showed a high loading capacity and provided a sustained drug release. These findings illustrate how the functionalisation of nanoparticles affect their physicochemical properties, which in turn determine their mucoadhesive properties and ability to penetrate mucus. They provide an important contribution to the field of mucosal drug delivery.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral