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Title: The synthesis and characterisation of dendritic macromolecules for drug delivery application
Author: Shamsudin, Suriani
ISNI:       0000 0004 2723 6208
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2012
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Today, drugs used in treating disease are almost all hydrophobic, which makes them unattractive for applying to patients. To overcome this problem, an amphiphilic macromolecule was designed which can deliver drugs to the specific targeted area. Therefore, this study focuses on the synthesis of water soluble hyperbranched polymers and their application in drug delivery systems. The first part of the thesis describes the synthesis of water soluble hyperbranched polymers by the anionic-polymerisation technique, with p-nitrophenol as the core and glycidol as the monomer. The core is important to control the molecular weight of the hyperbranched polymer. We then produced five different molecular weights by varying the core to monomer ratio, which produced hyperbranched polymers with molecular weights of 4000 Da, 8000 Da, 12500 Da, 27000 Da and 50000 Da, and four different concentrations of each molecular weight, 1.00 x 10-4 M, 2.00 x 10-4 M, 4.00 x 10-4 M and 6.00 x 10-4 M. To investigate the performance of the hyperbranched polymers, four different hydrophobic molecules were studied. The molecules were naphthalene, ibuprofen, tetracarboxyphenyl porphyrin (TCPP) and anti-prion drug. Encapsulation studies showed the concentration of each molecule increased with an increase in molecular weight and concentration of the hyperbranched polymer The functionalisation of folic acid on the surface of the hyperbranched polymer would enhance the effectiveness of the polymer as a drug delivery agent for targeting in cancer treatment. The above macromolecule was synthesised by conjugation with folic acid through poly (ethylene glycol) as spacer. The final chapter of this work describes the encapsulation of two hydrophobic molecules, ibuprofen and tetracarboxyphenyl porphyrin with water soluble PAMAM dendrimers. PAMAM dendrimers from G0.5 to G2.5 were synthesised. The results showed that more drug solubilised, the concentration of both molecules increased with an increase in dendrimer concentration. Then a comparison was made between encapsulation with water soluble hyperbranched polymers and water soluble PAMAM dendrimers. Similar molecular weight was used for both polymers of 4000 Da. For both polymers, the result demonstrated that the concentration of drug rose at 2.00 x 10-4 M and plateaued at a polymer concentration of 6.00 x 10-4 M. It was suggested the above trend was due to the aggregation of polymer. The above studies make a valuable contribution to the development of good drug delivery systems.
Supervisor: Lance, Twyman Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available