Black, Fiona E.
(1999)
The characterisation and interactions of biomedical polymers.
PhD thesis, University of Nottingham.
Abstract
As the world population grows and the standard of living increases a need for better health care is an important consideration. Over the latter half of this century the use of polymeric materials within the field of medicine has grown considerably.
This thesis investigates a variety of novel polymers whose applications within the medical field are both important and varied. In the cases studied, as with other polymeric materials intended for medicinal uses, the interaction with their surfaces is important, as when placed in the body the surface is the first place of contact and hence interaction with the system. Because of the importance of these surface interactions, which can elicit both beneficial and detrimental effects, this thesis is concerned with the surface chemistry and the relationship of this property to the interfacial interactions of the polymeric systems investigated.
Chapter 1 will concentrate on providing a historical overview of the field of polymers, especially the applications in the biomedical field. The surface analytical techniques of surface plasmon resonance (SPR), atomic force microscopy (AFM), X-ray photoelectron spectrometry (XPS) and secondary ion mass spectrometry (SIMS) utilised in this the is to investigate the surface properties of the materials of interest will also be introduced.
The demand for organ transplants far outweighs the supply of donor organs. Therefore, many patients with a variety of disease die each year. If new organs could be grown utilising the patients own cells, the supply of organs could be increased to meet the demand and these custom grown organ would not nave the problems of rejection as observed with donor ones. This is what tissue engineering aims to do. By utilising polymer matrices, to provide a scaffold for the tissue to grow in the correct configuration and a variety of growth factors and cell signalling agents to ensure the correct differentiation and function of the cells, it is hoped in the future new organs for example lung and livers will be able to be grown on demand. Chapter 3 and 4 concentrate on the in depth study of a polymer intended for such an application. Chapter 3 concentrates on determining the surface chemistry of this polymer system. XPS and SIMS are used to identify the type of chemical groups present at the surface and quantify their contribution to the overall surface layer. Chapter 4, probes the interactions, both specific and non specific with this system using a variety of complementary techniques. SPR is utilised to quantify the extent and rate of the interactions, whilst AFM in force distance mode the strength of these. AFM was also utilised to visualize the absorbed molecules on the polymer surfaces.
In Chapter 5 the area of gene therapy is introduced. It is hoped that in the future, gene therapy may form the basis of a cure for inherited gene tic diseases, such as hemophilia and other conditions such as AIDS and some cancers. The main problems which need to be overcome before this aim can be realised are firstly, isolating the correct genes to cure the diseases, and secondly, delivery of these genes. Cationic polymers and cationic lipids are two of the three main areas of research being investigated to find a potential carrier system for the DNA. In Chapter 5, the effect of PEG molecular weight on the condensation of plasmid DNA into a particles by poly(L-lysine)s for gene therapy is investigated. SPR was utilised to investigated the rate and extent of DNA binding and condensation by the various polymers, and utilising AFM the effect of PEG molecular weight on the structure of the observed particles was probed.
The gene therapy theme is continued in Chapter 6 where the surface interactions of a cationic lipid / DNA gene therapy complex is investigated by both AFM and SPR. There are two main aims to the studies in this chapter. Firstly, to provide an understanding of the interactions between the DNA and lipid components of the delivery system. It is hoped this will supply further information on its stability, formation and structure and secondly, to provide a knowledge of the interactions of the complex with model surfaces. This may provide an insight into the gene therapy vectors possible mode of interaction with the cell.
Chapter 7, is concerned with a family of dendrimeric polymers. The family of interest are the poly(amidoamine) (PAM AM) dendrimers. These have shown potential not only as drug delivery vehicles in the field of cancer chemotherapy and gene therapy, but also in enhancing medical imaging. The investigations performed in Chapter 7 form a basis for understanding the factors effecting the PAMAM's interaction with cell membranes and hence, provide information for optimising their formulation into drug delivery vehicles. The studies undertaken utilised both AFM and SPR as well as a range of model surface. These surfaces possess differing characteristics and were ulilised in conjunction with AFM and SPR to study the effect of dendrimer size, shape, surface charge and charge density on the interaction of these molecules.
The final chapter, Chapter 8 discusses the progress made towards the aims of this thesis as outlined in section 1.8 and addresses the avenues for future investigations exposed by experimental work in chapters 3 - 7. Overall it is hoped that the work described in this thesis shows that a multi technique approach, as well as the collaborations of chemists, materials engineers, biophysicist, biologists and clinicians may, in the future lead to a better understanding of the materials utilised in the medical setting and hence provide a systematic design of systems for treating specific disease conditions.
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