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dc.contributor.advisorObuobi, Sybil
dc.contributor.advisorSkalko-Basnet, Natasa
dc.contributor.authorPhung, Anna Ngoc
dc.date.accessioned2023-05-10T05:38:26Z
dc.date.available2023-05-10T05:38:26Z
dc.date.issued2021-05-10en
dc.description.abstractIn recent years, many pathogenic bacteria have developed resistance against the existing antimicrobials, a phenomenon known as antimicrobial resistance (AMR). One of the many reasons contributing to the observed failure of current therapies, is the poor drug penetration across the microbial biofilm. Biofilms are small structural communities of bacterial cells that excrete an extracellular polymeric substance. They are involved in the pathogenesis of many diseases and account for up to 80% of all human bacterial infections. Nanotechnology based drug delivery systems (DDS) can enhance the therapeutic efficacy of conventional antimicrobial drugs but very few possess responsiveness to the biofilm milieu. This project therefore seeks to develop a zwitterionic nanoparticle, which leverages on the biofilm microenvironment (i.e. acidic milieu, bacterial enzymes) to control the behavior of the DDS against Staphylococcus aureus biofilms. DNA nanogel loaded with vancomycin was fabricated by a two-step annealing method and incorporated into zwitterionic liposomes via the thin-film hydration method to prepare a series of zwitterionic nanoparticles. Characterization of the most optimal formulation was done by dynamic light scattering (DLS). In vitro drug release profile was evaluated in the absence/presence of lipase. Biofilm binding, penetration, inhibition and eradication using the formulations was evaluated via crystal violet staining, scanning electron microscopy (SEM) and confocal microscopy (CLSM). The toxicity and translational value of the formulation was evaluated against HaCaT cells and in an ex vivo porcine skin explant model respectively. The most optimal zwitterionic nanoparticle formulation, PDM 90/5/5, had an average size of 220.63 ± 0.84 nm, exhibiting a zeta potential of +0.02 ± 0.02 mV at physiologic pH and +15.23 ± 0.21 mV at acidic pH. Cumulative release of the PDM 90/5/5 formulation in presence of lipase 8 mg/mL was 88.76 ± 14.95% after 24 h compared to the release profile in the absence of lipase (49.57 ± 1.46%). PDM 90/5/5 effectively inhibited and eradicated S. aureus biofilms in vitro and ex vivo. Toxicity studies on HaCaT cells revealed negligible toxicity. In conclusion, zwitterionic nanoparticles able to enhance the delivery of vancomycin against S. aureus wound biofilms were successfully developed. The formulation demonstrated pH and enzyme responsiveness, enhanced biofilm binding and controlled the drug release. Key words: pH-responsive drug delivery systems; nanoparticles; DNA nanotechnology; liposomes; biofilm; wound infectionen_US
dc.identifier.urihttps://hdl.handle.net/10037/29179
dc.language.isoengen_US
dc.publisherUiT Norges arktiske universitetno
dc.publisherUiT The Arctic University of Norwayen
dc.rights.holderCopyright 2021 The Author(s)
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/4.0en_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)en_US
dc.subject.courseIDFAR-3911
dc.subjectFAR-3911en_US
dc.titleZwitterionic antimicrobial nanoparticles for biofilm therapyen_US
dc.typeMastergradsoppgaveno
dc.typeMaster thesisen


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Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)