Response surface modelling and investigation into release kinetics and in vivo toxicity of nanocellulose-based slow-release devices for delivery of quercetin

Simple item page
dc.contributor.advisorChimpango, AFAen_ZA
dc.contributor.advisorSmith, Carineen_ZA
dc.contributor.authorKeirsgieter, Hannahen_ZA
dc.contributor.otherStellenbosch University. Faculty of Engineering. Dept. of Mechanical and Mechatronic Engineering.en_ZA
dc.date.accessioned2022-11-18T10:43:04Zen_ZA
dc.date.accessioned2023-01-16T12:53:28Zen_ZA
dc.date.available2022-11-18T10:43:04Zen_ZA
dc.date.available2023-01-16T12:53:28Zen_ZA
dc.date.issued2022-11en_ZA
dc.descriptionThesis (MSc) -- Stellenbosch University, 2022.en_ZA
dc.description.abstractENGLISH ABSTRACT: The delivery of many anti-inflammatory and anti-cancer drugs is hindered due to their low solubility in water, leading to poor bioavailability and therapeutic efficacy. The high specific surface area and customisable properties of nanoscale materials have established them as innovative solutions in many biomedical applications, such as wound healing, tissue engineering and drug delivery. Nanocellulose (NC) in particular is of special interest as a drug carrier, due to its inherent biocompatibility, biodegradability, and low toxicity. This study focused on cellulose nanocrystals (CNC) and nanofibres (CNF), as potential drug delivery systems (DDSs) for slow-release of the model hydrophobic drug, quercetin. NC is naturally hydrophilic and anionic, and was therefore first modified with the cationic surfactant, cetyltrimethylammonium bromide (CTAB), in order to facilitate effective drug binding through hydrophobic interaction. The effect of surfactant and drug concentration on particle size (Z), polydispersity index (PdI), zeta potential (ζ) and binding efficiency (BE) was investigated by response surface methodology (RSM), an empirical modelling technique in parametric optimisation. A design of experiments (DOE) approach was taken to obtain the experimental data, through a full factorial design (FFD), followed by a central composite design (CCD). The regressed Z and PdI models for both designs reported R2 values < 75%, while the ζ and BE models reported mean R2 values of 78% and 90%, respectively, indicating good model fits. The optimal responses for CNC were reported as Z = 5436 nm, PdI = 0.56, ζ = – 18.3 mV, and BE = 76.9%, at a CTAB and quercetin concentration of 3.3 mM and 4.2 mg/mL, respectively. The optimal responses for CNF were reported as Z = 4183 nm, PdI = 0.56, ζ = – 14.3 mV, and BE = 80.8%, at a CTAB and quercetin concentration of 2.0 mM and 5.1 mg/mL, respectively. Design validation resulted in experimental errors of 18.2% for CNC and 9.9% for CNF. Characterisation of the DDSs was performed by dynamic light scattering (DLS) using a Malvern Zetasizer, and further investigation into particle morphology was carried out by scanning electron microscopy (SEM). The in vitro quercetin release profile of a CNC-CTAB-QT formulation was tested using the dialysis bag method, and best fitted by the Korsmeyer-Peppas model (R2 = 99.9%), with a release exponent n > 1 suggesting super case II (non-Fickian) transport. In the first hour, the DDS exhibited a delayed cumulative release of 29%, compared to the cumulative release of 62% by the free drug. The in vivo safety profile of this formulation was evaluated by performing a toxicity assay on zebrafish larvae, but was constrained by excessive aggregation in the incubation medium.en_ZA
dc.description.abstractAFRIKAANS OPSOMMING: Die lewering van talle anti-inflammatoriese en anti-kankermiddele word verhinder deur hul lae oplosbaarheid in water, wat tot swak biobeskikbaarheid en terapeutiese doeltreffendheid lei. Die hoë spesifieke oppervlakte en pasmaakbare eienskappe van nanoskaalmateriale beteken dat hulle innoverende oplossings in talle biomediese toepassings, soos wondgenesing, weefselontwikkeling en middellewering, is. Nanosellulose is spesifiek van belang as ʼn middeldraer weens die inherente bioversoenbaarheid, bio-afbreekbaarheid en lae toksisiteit daarvan. Hierdie studie het gefokus op sellulose nanokristalle (SNK) en sellulose nanovesels (SNV) as moontlike middelleweringstelsels (MLS’e) vir stadige vrystelling van die model- hidrofobiese middel kwersetien. Nanosellulose is van nature hidrofilies en anionies, en is dus eerste met die kationiese surfaktant setieltrimetielammoniumbromied (STAB) gemodifiseer om doeltreffende middelbinding deur hidrofobiese interaksie in die hand te werk. Die uitwerking van surfaktant- en middelkonsentrasie op deeltjiegrootte (Z), polidispersiteitsindeks (PdI), zeta-potensiaal (ζ) en bindingdoeltreffendheid (BD) is met behulp van responseoppervlakmetodologie, ʼn empiriese modelleringstegniek in parametriese optimering. ʼn Eksperimentontwerptegniek word toegepas om die eksperimentele data te verkry, deur ʼn volledige faktoriale ontwerp, gevolg deur ʼn sentrale saamstellingsontwerp. Die geregresseerde Z en PdI modelle vir albei ontwerpe het R2 waardes < 75% gelewer, terwyl die ζ en BD modelle gemiddele R2 waardes van onderskeidelik 78% en 90% gelewer het, wat goeie modelpassings toon. Die optimale response vir SNK was Z = 5436 nm, PdI = 0.56, ζ = – 18.3 mV en BD = 76.9% teen ʼn STAB- and kwersetien-konsentrasie van onderskeidelik 3.3 mM en 4.2 mg/mL. Die optimale response vir SNV was Z = 4183 nm, PdI = 0.56, ζ = – 14.3 mV en BD = 80.8% teen ʼn STAB- and kwersetien-konsentrasie van onderskeidelik 2.0 mM en 5.1 mg/mL. Ontwerpbekragtiging het gelei tot eksperimentele foute van 18.2% vir SNK en 9.9% vir SNV. Karakterisering van die MLS’e is uitgevoer deur dinamiese ligverstrooiing met behulp van ʼn Malvern Zetasizer, en verdere ondersoek na deeltjiemorfologie is deur skanderingselektronmikroskopie uitgevoer. Die in vitro-kwersetien-vrystellingsprofiel van ʼn SNK-STAB-QT-formulering is met die dialisesakmetode getoets, en was die beste passing vir die Korsmeyer-Peppas-model (R2 = 99.9%), met ʼn vrystellingseksponent van n > 1 wat supergeval II (nie-Fickiaanse) transport aan die hand doen. In die eerste uur het die MLS ʼn vertraagde kumulatiewe vrystelling van 29% getoon, in vergelyking met die kumulatiewe vrystelling van 62% deur die vrye middel. Die in vivo-veiligheidsprofiel van hierdie formulering is geëvalueer deur die uitvoer van ʼn toksisiteitstoets op sebravis-larwes, maar is deur uitermatige klomping in die inkubasiemedium beperk.af_ZA
dc.format.extentxv, 97 pages : illustrationsen_ZA
dc.identifier.urihttp://hdl.handle.net/10019.1/126166en_ZA
dc.language.isoen_ZAen_ZA
dc.publisherStellenbosch : Stellenbosch Universityen_ZA
dc.rights.holderStellenbosch Universityen_ZA
dc.subjectSurface active agentsen_ZA
dc.subjectAnti-inflammatory agents – Bioavailabilityen_ZA
dc.subjectNanofibersen_ZA
dc.subjectQuercetin—Therapeutic useen_ZA
dc.subjectCellulose nanocrystalsen_ZA
dc.subjectUCTDen_ZA
dc.titleResponse surface modelling and investigation into release kinetics and in vivo toxicity of nanocellulose-based slow-release devices for delivery of quercetinen_ZA
dc.typeThesisen_ZA
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
keirsgieter_response_2022.pdf
Size:
4.8 MB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Masters Degrees (Mechanical and Mechatronic Engineering)