The work presented in this thesis explores the use of electrohydrodynamic atomisation as a one-step method for the fabrication of monodispersed poly(lactic acid) and poly(lactic-co-glycolic) nanoparticles designed for selective delivery of anti-cancer drugs. Following optimisation studies of the relevant electrospray parameters, a range of PLA and PLGA nanocarriers loaded with the anti-cancer drug doxorubicin and with folic acid (aimed at achieving tumour targeting) was prepared and characterised using dynamic light scattering, electrophoretic mobility measurements, and confocal and atomic force microscopy. Unloaded and/or selectively loaded nanoparticles were also fabricated using the same technique and employed as controls. It was found - for all nanoparticles tested - that sensible yield, minimal size and polydispersity were obtained when using dimethylsulphoxide and dichloromethane with an optimal collection distance of 15 cm, applied voltage 9.2 – 9.6 kV and flow rate 10 μL/min. Nanoparticles were further tested in vitro for their interactions with human cells in terms of toxicity, tumour selectivity and cellular uptake, by using a range of techniques that include cytotoxicity assays, confocal microscopy, live-cell imaging and flow cytometry. When compared to the results obtained with normal human cells (16HBE), those attained using human cancer cells that overexpress folate receptors (CALU-3) indicated an increased cytotoxic effect of the loaded nanoparticles. Furthermore, cellular uptake studies demonstrated significant selectivity of the nanoparticles loaded with both doxorubicin and folic acid for the CALU-3 cell line compared to normal 16HBE cells.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:686957 |
| Date | January 2015 |
| Creators | Smith, Ashleigh |
| Contributors | Barbu, Eugen ; Van Der Merwe, Susanna Maria ; Tsibouklis, John |
| Publisher | University of Portsmouth |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://researchportal.port.ac.uk/portal/en/theses/electrohydrodynamic-atomisation-produced-nanoparticles-for-the-targeted-delivery-of-cancer-chemotherapeutics(7cdcfbeb-4ff4-4282-9cdf-c1dc2f261162).html |
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