Development of multifunctional calcium phosphate particles for drug delivery and formation of cross-linked materials

Williams, Richard Lee (2014). Development of multifunctional calcium phosphate particles for drug delivery and formation of cross-linked materials. University of Birmingham. Ph.D.

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Abstract

Calcium phosphates (CaPs) have been used extensively as bone replacement materials, substrates for drug release and transfection agents because of their non-cytotoxic nature and chemical similarity to the mineral component of human bone. However, biomolecule attachment to CaPs usually rely upon adsorption, which can lead to inconsistent coverage and variable release, and the fate of CaPs upon cellular internalisation is not fully understood. The difficulty in tracking the particles can be related to the visual similarity to granulation within the cells.

This thesis sought to functionalise the surface of CaP particles to enable the engraftment of biomolecules onto the particle surface and the formation of a cross-linked matrix. The engraftment of a thiol-reactive fluorescent dye gave visual confirmation that molecules can be bound to the surface and enabled silicon-substituted hydroxyapatite (SiHA) particle tracking within MC3T3 cells. Volume and size distribution analysis suggested that internalised particles larger than 1μm, but not encapsulated within lysosomes, correlated with observations of cell death. The method was expanded for other CaPs and demonstrated through engraftment of a novel antimicrobial peptide, which was shown to be more effective at preventing biofilm formation than surface adsorbed peptide, and the fabrication of a new organic/inorganic composite.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):