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Title: Investigation of cellular and molecular mechanisms involved in targeted drug delivery systems for human cancers
Author: Kaur, Davinder
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2002
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CytocapsTM are a potential drug delivery system comprising of approximately 3-micron human serum albumin microcapsules with doxorubicin covalently linked to their outer surface. In the present study this drug delivery system was investigated in vitro using a combination of cytometric techniques including flow cytometry, Laser scanning cytometry, fluorescent microscopy and high performance liquid chromatography to investigate the binding of CytocapsTM and uptake of doxorubicin in both adherent (MCF-7/Wild type (WT), MCF-7/doxorubicin resistant (R) and EA.hy926) and non-adherent (HL-60 and Jurkat) cancerous cell lines. With all cells studied CytocapsTM appeared to act by releasing small amounts of drug which was taken up and then processed by the cells and responded in very similar ways to cell incubated with free drug. CytocapsTM bound to adherent cells (albeit to a sub-set of the population) but not non-adherent cell lines or peripheral blood cells. Whilst this study only investigated a limited number of cell types it would be logical to conclude that the binding of CytocapsTM to adherent cells was found to be generalised phenomenon. The efficacy of doxorubicin CytocapsTM was similar to free doxorubicin in terms of dosage. CytocapsTM were unable to overcome multiple drug resistance in the MCF-7/R cell line despite the entry of CytocapsTM into the cells at 72-168 hour incubations. Despite the different patterns of drug uptake in all the different cell types (excluding the MCF-7/R cells) comparable concentrations (0.5mM) of either CytocapsTM or free doxorubicin produced a predominantly cytostatic effect in the cells rather than a cytotoxic effect. In conclusion, CytocapsTM prove to be an effective mechanism for delivery of doxorubicin. Their interaction with adherent MCF-7/WT, MCF-7R and EA.hy926 cells could prove to be beneficial and could be used in the treatment of solid aggressive cancers where the CytocapsTM would be able to penetrate the different layers of cells by exerting their effect in the core of the tumour.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available