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Title: Phosphorylated nanoaggregates as multifunctional agents in oral health
Author: Harper, Robert Anthony
ISNI:       0000 0004 6347 8650
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2017
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Oral microbial disease is highly prevalent globally and is being associated with a multitude of systemic illnesses. There is a vast range of oral health products containing tooth hardening and antimicrobial agents yet the problem persists. The aim of this thesis was to chemically modify the anti-inflammatory vitamin E in order to introduce novel substantive antimicrobial activity giving it multifunctional activity to combat oral disease. (+) Alpha tocopherol (α-T) was chemically modified by phosphorylation to generate (+) alpha tocopheryl phosphate (α-TP). (+) α-TP was observed to form nano sized aggregates with a μM critical aggregation constant when dispersed in Tris buffer. The addition of the phosphate group was found to introduce substantive antimicrobial activity as (+) α-TP retarded Streptococci biofilm growth, adhered to hydroxyapatite and inhibited salivary biofilm growth whilst (+) α-T did not. This activity was related to nanostructure architectures as (+) α-T formed spherical, non-surface adherent liposomes (563 ± 1 nm, -10.5 ± 0.2 mV) whilst (+) α-TP formed surface adherent, planar bilayer islands (175 ± 21 nm, -14.9 ± 3.5 mV). Tris facilitated (+) α-TP antimicrobial activity as when it was dispersed in phosphate buffer it did not penetrate, kill or retard biofilm bacterial growth. This was shown to be due to the presence of the ions affecting bacterial membrane packing, aggregate packing and aggregate charge. The small monolayer pressure increase of the (+) α-TP bilayer planar island interactions suggested the antibacterial mechanism was not likely to be simple lyses, but perhaps internalisation and enzymatic inhibition. The (+) α-TP bilayer planar islands swelled into micron sized aggregates when dispersed in cell culture media, selectivity killed macrophages and selectively inhibited monocyte chemoattractant 1 production from human gingival fibroblast cells. The strategy of utilising phosphorylated vitamin E nanoaggregates as multifunctional agents in oral health described herein represents a potential technology platform worthy of clinical evaluation.
Supervisor: Jones, Stuart Allen ; Hider, Robert Charles Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available