Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.791421
Title: Computational and experimental studies on the formation of polymer-drug nanoparticles
Author: Styliari, Ioanna Danai
ISNI:       0000 0004 8502 2136
Awarding Body: University of Nottingham
Current Institution: University of Nottingham
Date of Award: 2017
Availability of Full Text:
Access from EThOS:
Full text unavailable from EThOS. Restricted access.
Access from Institution:
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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.791421  DOI: Not available
Keywords: RS Pharmacy and materia medica
Share: