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Title: Polyacrylamide nanoparticle delivery systems in photodynamic therapy
Author: Kuruppuarachchi, Maheshika
ISNI:       0000 0004 2721 0577
Awarding Body: University of Hull
Current Institution: University of Hull
Date of Award: 2011
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In treating many diseases, including cancer and bacterial infections, drug resistance has emerged as a major obstacle limiting the therapeutic efficacy of chemotherapeutic agents. One area which may prove to be particularly attractive is Photodynamic Therapy (PDT). Reactive oxygen species (ROS) which cause damage to tumour tissue are not generated until the drug is activated by light, minimising generalised toxicity and giving a high degree of spatial control over the clinical effect. The application of nanoparticles (NPs) in the field of drug delivery is extensively studied as a potential for delivering high payloads of drugs site selectively. They can be targeted towards, and accumulate in, tumour tissue by the enhanced permeability and retention effect, if sequestration by the reticuloendothelial system (RES) is avoided. This project aimed to develop an efficient drug delivery system based on nano-sized particles. Polyacrylamide nanoparticles were chosen to deliver photosensitisers due to the chemical and biological inertness of polyacrylamide, in addition to its optical transparency. The porous three-dimensional particles produced from microemulsion polymerisation reactions are typically prepared in the nanometre range. In the study, two types of NPs loaded with photodynamic sensitisers are synthesised: photosensitiser (i.e. phthalocyanine) entrapped NPs (PCNP) and photosensitiser (i.e. phthalocyanine) entrapped NPs coated with a second photosensitiser (i.e. porphyrin) (PCNP-P) to enhance the capacity for ROS generation, and hence therapeutic potential. The mean sizes of these particles were 45±10nm and 95±10nm respectively. NP uptake by human Caucasian colon adenocarcinoma cells (HT29) was determined by flow cytometry and confocal microscopy. Cell viability assays using two chosen NPs (PC-NP and PCNP-P) corresponding to the minimum uptake time (<5 minutes) and maximum uptake time (25 hours), quantified by flow cytometry, demonstrated that these cancer cells can be damaged by activation of the photodynamic NPs both when in the external media and post internalisation. Results suggest that in order to induce photodynamic damage, the NPs need only be associated with the tumour cell closely enough to deliver singlet oxygen - their internalisation within target cells may not be necessary. Clinically, this could be of great importance as it may help to combat the ability of many cancer cells to actively expel conventional anti-cancer drugs.
Supervisor: Boyle, Ross; Archibald, Steve Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Chemistry