Nanofabrication and Engineering of Gene Delivery Vectors

Abstract

Coaxial electrospray is an encapsulation method in use in biomedical research for the encapsulation of drugs and genes. In this thesis, its ability to produce polymer capsules with a core-shell structure was investigated as potential non-viral vector for gene delivery. Three main aspects were considered. 1) The shell polymer was varied between a homopolymer and block copolymer to compare their ability to condense the inner polymer and so produce a smaller particle. 2) DNA is expensive and not cost-effective to use in the large quantities required here. Therefore two different polymers (carboxymethyl cellulose and hyaluronic acid, referred to as CMC and HA respectively) were used for the inner polymer and as potential cost-effective models for DNA due to their similar structures – long-chain polymers with a negative charge. 3) Electrosprayed particles were characterised and compared with bulk-assembled complexes to assess differences in size, structure and zeta potential. For electrospray to be considered as a good method, it must produce particles with characteristics that are at least as good as complexes produced through self-assembly. It was seen that electrospray was able to produce particles of a similar size to bulk-assembled complexes (110 nm and 106 nm respectively) and core-shell structures were seen with all particles and complexes. The main differences were seen with zeta potential. Complexes using the block copolymer decreased the zeta potential to a large degree, but this decrease was not seen with electrosprayed particles suggesting a difference in shell structure. Particles and complexes containing hyaluronic acid were seen to be less stable than those containing CMC as they underwent aggregation in aqueous phase. Finally it was seen that the particles produced by electrospray were relatively soft as they underwent deformation when sprayed onto hard substrates.