Papanicolaou, Irene;
(2005)
Liposome-polymer nanoparticle hybrids as vectors in dna vaccine delivery.
Doctoral thesis (Ph.D.), University College London.
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Abstract
The use of cationic liposomes and biodegradable polymer particles as vehicles for DNA vaccine delivery has long been established. Both systems, however, have limitations in the form of instability in the biological medium and low DNA loading efficiency respectively. Attempts to address the weaknesses of the two systems have led researchers to the development of hybrid lipid-polymer vectors that aim to combine their strengths. In this work, the cationic liposome and biodegradable polymer delivery system were combined in order to generate a hybrid DNA vaccine vector of improved in vitro stability. Liposome-DNA complexes were treated with a selection of both hydrophobic and hydrophilic polymers and the properties of the resulting hybrid particles were investigated. The process did not appear to affect DNA loading, which remained high at 100%, the same as untreated liposome-DNA complexes. Exposure of the polymer-liposome formulations to nucleases in the presence of plasma revealed that polymer modification results in protection of the DNA from nuclease attack compared to untreated liposomes. The particles were also found to be resistant to polyelectrolyte exchange reactions. Therefore, the liposome-polymer nanoparticle hybrids that were generated successfully combined the strengths of their components in vitro. In order to determine which of the hybrid formulations that were produced was the most suitable for DNA vaccine delivery, the hybrids were evaluated further, initially in cell culture and then as DNA vaccine carriers in the mouse model. Cell culture studies showed that the most hydrophobic and cationic hybrids gave the highest transfection efficiencies. However, when tested in vivo, the hydrophobic and cationic hybrids were ineffective. Instead, it was the hydrophilic hybrids that were successful in eliciting an immune response, suggesting that they hold promise in the field and warrant further investigation.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D. |
| Title: | Liposome-polymer nanoparticle hybrids as vectors in dna vaccine delivery. |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis Digitised by Proquest. |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10122306 |
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