Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.695817
Title: Using nanomaterials to manipulate drug aggregation in order to enhance passive transmembrane transport
Author: Cai, Xiulian Jesmine
ISNI:       0000 0004 5991 2450
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2016
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Abstract:
Topical nanomaterials can enhance the passive diffusion of therapeutic agents into biological tissues but the mechanism by which they function is not yet fully understood. The aim of this study was to elucidate the interactions between the model drug tetracaine and the surfaces of nanomaterials with the view to understand and optimise the transmembrane transport process. Tetracaine was observed to form aggregates in aqueous solutions in the μM range and this aggregation process changed its percutaneous permeation. Nanoparticles co-administered on the membrane surface upon drug application were shown to manipulate the drug aggregation, thereby enhancing transmembrane transport. Tetracaine adsorbed strongly to the surface of carboxylmodified polystyrene nanoparticles (NanoPSCOOH) and minimally to silica nanoparticles (NanoSiO₂ ). The NanoSiO₂ enhanced tetracaine transport by 3.6-fold while the NanoPSCOOH hindered tetracaine transport, leading to the conclusion that a mild perturbation of the tetracaine aggregation by a nanoparticle surface produced the most interesting effects in terms of transmembrane transport. These results were translated to a topical HPMC spray formulation. The co-administration of HPMC tetracaine spray formulation with NanoSiO₂ enhanced tetracaine transport by 95-fold, improved accumulative by 307-fold and reduced the lag time by 15.6-fold when compared to the commercially available Ametop. The superiority was attributed to the NanoSiO₂ breaking of tetracaine aggregates, known to hinder permeation. In addition, the decrease in formulation macroviscosity was hypothesized to have reduced drugvehicle interactions and thus facilitate permeation. The strategy of utilising nanomaterials to manipulate drug aggregation described herein represents a potential technology platform worthy of clinical evaluation.
Supervisor: Jones, Stuart Allen ; Mesquida, Patrick Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.695817  DOI: Not available
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