Abstract
The work presented in this thesis explores the use of electrohydrodynamicatomisation 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.
| Date of Award | 2015 |
|---|---|
| Original language | English |
| Awarding Institution |
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| Supervisor | Eugen Barbu (Supervisor), Marisa Van Der Merwe (Supervisor) & John Tsibouklis (Supervisor) |