2018AbdBHPhD.pdf (5.85 MB)
Molecularly Imprinted Polymers for Drug Delivery
thesisposted on 2018-11-08, 15:40 authored by Bashar H. Abd
Molecularly imprinted polymers (MIP) have received much attention and increased interest thanks to their excellent cost efficiency, robustness, high selectivity and simple short synthesis. The molecular imprinting process can be defined as creation of molecular recognition sites in a synthetic polymer. The template-derived sites thus created within the polymeric matrix allow MIP to selectively recognise and bind the target molecule. In light of these properties, MIP have been successfully applied in sensors, assays separation, and for drug delivery applications. Because of their small size, MIP nanoparticles (MIP NPs) can be used in biomedicine as specific drug delivery device, since the nanoscale format is potentially suitable for cellular or in vivo applications. This work has demonstrated that MIP NPs could be used as carriers for targeted drug delivery. For this purpose, the anti-inflammatory and anti-cancer agent curcumin was selected to develop a high throughput screening method which allows to optimise the controlled delivery of drugs using magnetic MIP NPs. Senescent cells which contribute to a number of pathophysiological conditions including fibrosis, diabetes, cancer, Alzheimer’s and ageing, were selected as a model system to demonstrate the ability of specific MIP NPs to recognise them and deliver the cytotoxic drugs. Fluorescent MIP NPs specific for two epitopes of senescent cells B2M and DEP were prepared and characterised. In vitro tests based on two human cell lines have demonstrated the ability of the developed MIP NPs to recognise the senescent cells and confirmed that they were not toxic to the cells. In order to demonstrated the targeted drug delivery double-imprinted fluorescent MIP NPs with binding site specific for senescent cells and containing cytotoxic drugs Dasatnib and Gramicidin have been produced. In vitro tests with groups of old and young mice injected with MIP NPs demonstrated the targeted induction of cell death. It is possible to conclude that fluorescent MIP NPs could be effectively used as imaging tool for in vitro analysis as well as carriers for targeted delivery of the drugs in vivo. The protocols developed in this work are applicable for any other targets of clinical importance.
Supervisor(s)Piletska, Elena; Piletsky, Sergey
Date of award2018-10-30
Author affiliationDepartment of Chemistry
Awarding institutionUniversity of Leicester