Synthesis of imprinted polymers for the detection of tamoxifen or its metabolites and evaluation of their potential as drug carriers.

Abstract

Recent advances in the area of nanotechnology have led to interesting applications of nanomaterials in medicine, especially in the areas of imaging and treatment. This thesis presents the development of two molecularly imprinted polymers (MIPs) based on the same fluorescent functional monomer. One MIP, prepared in the bulk format, is investigated for its ability to detect tamoxifen and its metabolites. The other MIP synthesised in the nanogel format, holds the potential to be used as pH-responsive drug delivery system. Four objectives were identified within this project. The first was the design and synthesis of fluorescent functional monomer. Two coumarin derivatives carrying a polymerisable unit, for covalent bonding within the polymer, and a carboxylic moiety, for interaction site with the template, were synthesised and characterised. However, only one of them (the VCC: 6-vynilcoumarin-4-carboxylic acid) showed high fluorescent yield and was selected as functional monomer. The second objective involved the development of a detection system based on bulk MIP containing the VCC fluorescent monomer. This system proved effective in generating a detectable signal upon binding the analytes. The signal was observed as a quenching of the polymer fluorescence and it was proportional to the amount of target molecules detected. The third objective was the preparation of tamoxifen-imprinted nanogels for potential application in the drug delivery field. The optimisation of the procedure gave a set of NIP/MIP with the desired solubility, particle size and fluorescence emission. These nanogels were then employed in the last objective, which involved the toxicity study and evaluation of the drug loading on of transgenic line of zebrafish. The nanogels were non-toxic at the tested concentrations and the presence of tamoxifen was confirmed.