Investigation Into The Use Of Molecularly Imprinted Polymer Nanoparticles For The Delivery Of Therapeutic Compounds

Abstract

Due to the increasing popularity of the use of molecularly imprinted polymer (MIP) nanoparticles as diagnostic tools, recently, interest has been directed to the use of MIP nanoparticles for use as a drug delivery system. MIPs are ideal as they are cheap to manufacture, highly stable and robust. Nanoparticles used for drug delivery work either by a triggered release of a payload under certain conditions or by controlled release out of the nanoparticles. The use of controlled release reduces the dosage of drug required to be effective on an illness or disease; it also reduces unwanted side effects caused by medication as a smaller dosage is needed compared to drugs administered by a conventional route. Initially, methods of nanoparticle sterilisation were investigated, due to the development of contamination in liquid solutions. This can cause complications when injected into live tissues. Testing found that the use of trehalose at 10mg/mL demonstrated the smallest change in nanoparticle properties, while sterilisation was found to have minimal effect on the nanoparticle properties (Chapter 2). To determine the ability of polymer nanoparticles to enter into cells, siRNA transfection studies utilising caspase-3 siRNA were carried out with the siRNA loaded onto the nanoparticles employing a charge-based interaction. The results showed that the optimal nanoparticle species was as efficient as the control transfection agent (Chapter 3). Subsequently, molecularly imprinted nanoparticles were tested for the controlled release of doxorubicin over time from different types of nanoparticles. Initially, doxorubicin imprinted magnetic core nanoparticles were tested and compared to non-imprinted nanoparticles. The results showed that the use of 2-hydroxymethyl acrylate as the functional monomer demonstrated the lowest rate of release of doxorubicin over time (Chapter 4). Solid phase synthesised were then tested with both vancomycin and EGFR binding peptide as the primary templates, the nanoparticles produced with 1mg of doxorubicin in the polymerisation mixture of the vancomycin templated nanoparticles demonstrated the lowest rate of release. With the EGFR binding peptide nanoparticles, the nanoparticles produced in aqueous solvent demonstrated the lowest rate of doxorubicin release in comparison to the organic solvent synthesised nanoparticles (Chapter 5). The effect of the primary template presence on the nanoparticles was tested and demonstrated that the presence increases the rate and amount of doxorubicin release compared to no template being present (Chapter 6). The final stage was to test the effect of different levels of cross-linking by increasing the amount of cross-linking monomer in the polymerisation mixture and found that increasing the amount of cross-linking monomer by 25 x decreased the rate and amount of doxorubicin released over time. When the effect of template presence was tested against the amount of cross-linking monomer, it was found that the presence of vancomycin caused a small increase in the rate and amount of doxorubicin released (Chapter 7). Overall the nanoparticles demonstrated significant potential for use as a delivery vessel for doxorubicin for a controlled release into the cells