[Truncated abstract] Nascent research into nanomaterial toxicity indicates significant deviations from the parent material, with concerns regarding the potential of nanomaterials to cross biological barriers and enter into cells and organelles due to their small size. This thesis sets out to prove the hypothesis that chitosan nanoparticles could induce cytotoxicity in human intestinal and liver cells. Chitosan nanoparticles were evaluated because extensive research into their biomedical applications was based largely on the biodegradable and biocompatible profile of chitosan. In order to evaluate cytotoxicity, a novel method for the reproducible fabrication of a continual supply of chitosan nanoparticles (NP) was first developed using the spinning disc processing (SDP) technology. NP with a diameter of 20 ± 3 nm and zeta potential of 53.3 ± 4.3 mV were successfully produced, and were comparable to those produced by the conventional method. Particle size was modulated by the type and concentration of acid used in the chitosan feed solution. NP following dialysis and lyophilisation were stable in size when stored in the dry state at -20 C for up to 2 months. Dispersion of the lyophilised NP into various biorelevant media affected particle size, zeta potential and aggregation status. NP particle size was preserved in Hanks balanced salt solution and supplemented culture media, although protein adsorption in the latter caused the NP to assume a negative zeta potential. Evidence of particle aggregation was noted in phosphate buffered saline. NP toxicity against human intestinal cells was studied using the Caco-2 cell model and chitosan (Cs) as control at pH 7.4 (physiological) and pH 6.0 (upper GI).
|Qualification||Doctor of Philosophy|
|Publication status||Unpublished - 2010|