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Styliari, Ioanna Danai (2017) Computational and experimental studies on the formation of polymer-drug nanoparticles. PhD thesis, University of Nottingham.

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Abstract

Polymer based nanoparticle formulations attract attention as potentially highly tunable drug delivery systems. Interfacial deposition is a well-established technique, based on solvent displacement that is being used to form both polymer nanoparticles, as well as drug loaded polymer nanoparticles.

However currently, there is limited understanding of the underlying polymer - nanoparticle assembly mechanisms and this limits our ability to rationally design and optimise them. At the same time, conventional methods for the preparation of polymer-drug nanoparticles suffer from low encapsulation efficiencies and drug loadings, making them undesirable to the pharmaceutical industry.

In this thesis, a method used to polymer-coat the surface of iron oxide nanoparticles was translated to produce polymer-coated drug nanoparticles. In order to provide an holistic overview of the system and the underlying phenomena, both computational and experimental methods were used.

More particularly, all atom molecular dynamics simulations were employed to study the behaviour of the drug nanoparticles and the polymers during the interfacial deposition method. The system was built as a biphasic model, containing an aqueous-drug loaded-phase and an organic-polymer rich-phase. The model was a miniature in the atomistic level of the expected experimental set-up, keeping the ratios and concentrations as close as possible to pre-existing iron oxide nanoparticle work.

On a parallel path, experimental studies were performed. The polymers were synthesised and fully characterised. Then, the formation of drug-free polymer nanoparticles via the method was studied and the properties of these nanoparticles were analysed. Interestingly, when the drug was introduced into the method in the form of drug microparticles suspended in the aqueous region, polymer-coated drug nanoparticles were produced. These nanoparticles were stable, significantly different to the drug-free polymer nanoparticles and were characterised for their size and morphology. Further analysis of the polymer-coated drug nanoparticle suspensions revealed high encapsulation efficiencies and impressive drug loadings.

We conclude with some proposed future work on modelling polymer-based drug delivery systems, moving towards a “structure based formulation design” to complement the process of “structure based drug design” which is already very well established in the pharmaceutical industry.

Item Type:	Thesis (University of Nottingham only) (PhD)
Supervisors:	Laughton, Charles Garnett, Martin Alexander, Cameron
Keywords:	computational modelling, polymer drug nanoparticles, modified interfacial deposition, molecular dynamics
Subjects:	R Medicine > RS Pharmacy and materia medica
Faculties/Schools:	UK Campuses > Faculty of Science > School of Pharmacy
Item ID:	41132
Depositing User:	Styliari, Ioanna
Date Deposited:	19 Nov 2019 08:39
Last Modified:	06 May 2020 13:02
URI:	https://eprints.nottingham.ac.uk/id/eprint/41132

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