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dc.contributor.advisorMcDowell, Arlene
dc.contributor.advisorHook, Sarah
dc.contributor.authorVu, Thi Hong Hanh
dc.identifier.citationVu, T. H. H. (2019). Preparation and evaluation of oral nanoformulations containing antioxidant rutin (Thesis, Doctor of Philosophy). University of Otago. Retrieved from
dc.description.abstractPurpose Oxidants induce oxidative stress in the body playing an important role in the development of diseases such as cancer, arthritis, cardiovascular and neurological disease. Rutin - a strong antioxidant - can scavenge oxidants and reduce oxidative stress. Therefore, rutin has the potential to be used in the prevention and treatment of various diseases. However, the pharmacological effects of rutin administered via the oral route are limited because of its low solubility and poor oral bioavailability. The aim of this study was to produce and characterize rutin nanoparticles and to then assess their pharmacological effects, including antioxidant, anti-inflammatory and liver protection activities using zebrafish as a novel model. Methods Rutin nanoparticles of different composition were prepared. Rutin loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles were prepared using the single emulsion evaporation method and optimized using a design of experiments approach. Rutin liposomes and rutin phytosomes were produced by the thin film hydration method, and all particles were characterized. Finally, the in vitro release of rutin from nanoparticles was investigated in different biorelevant dissolution media. Rutin nanoparticles were examined for their ability to induce in vivo effects using a zebrafish model. Uptake of nanoparticles of different composition were investigated in vivo in the whole zebrafish and specifically in the liver. Finally, the antioxidant, anti-inflammatory and liver protective effects of rutin nanoparticles were examined by investigating changes in specific biomarkers. Results Rutin PLGA nanoparticles (size 179±13 nm, zeta potential -15±3 mV and entrapment efficiency of 27±2%) were prepared with interactions being detected between rutin and the PLGA polymer. Rutin was released slowly from PLGA nanoparticles with less than 10% being released over 5 h in biorelevant media. Rutin liposomes (size 147±10 nm, zeta potential 4.9±0.7 mV and entrapment efficiency of 17±10%) and rutin phytosomes (size 134±7 nm, zeta potential 0.7±0.5 mV and entrapment efficiency of 24±2%) were also produced and characterised. A hydrogen bond was detected between rutin and the phospholipid in rutin phytosomes, however, this was not observed in rutin liposomes. The release of rutin from liposomes and phytosomes in biorelevant media was low less than 10% and no difference was observed between the two formulations. Assessment of in vivo activity showed that nanoparticles with different compositions can be taken up into whole zebrafish embryos and into the liver via oral administration, with a higher uptake observed for the lipid-based formulations. Rutin and rutin nanoparticles were able to reduce levels of oxidant enzymes including superoxide dismutase (SOD) and catalase (CAT). Conclusion Rutin can be encapsulated in nanoparticles of different composition with mean sizes of less than 200 nm. Rutin was found to be changed from the crystalline form to the amorphous form when rutin was encapsulated in the nanoparticles. A hydrogen bond that formed between rutin and phospholipid in rutin phytosomes did not have any impact on drug loading, release or anti-oxidant activity. Rutin nanoparticles can be taken up in to zebrafish embryos and the liver, and had antioxidant activity, therefore rutin nanoparticles can be used as drug delivery system for rutin to improve bioavailability.
dc.publisherUniversity of Otago
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dc.titlePreparation and evaluation of oral nanoformulations containing antioxidant rutin
dc.language.rfc3066en of Pharmacy of Philosophy of Otago
otago.openaccessAbstract Only
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