Masters Degrees (Mechanical and Mechatronic Engineering)

Permanent URI for this collection

https://scholar.sun.ac.za/handle/10019.1/781

Browse

Browsing Masters Degrees (Mechanical and Mechatronic Engineering) by browse.metadata.advisor "Chimpango, AFA"

Now showing 1 - 1 of 1
  • Thumbnail Image
    Item
    Response surface modelling and investigation into release kinetics and in vivo toxicity of nanocellulose-based slow-release devices for delivery of quercetin
    (Stellenbosch : Stellenbosch University, 2022-11) Keirsgieter, Hannah; Chimpango, AFA; Smith, Carine; Stellenbosch University. Faculty of Engineering. Dept. of Mechanical and Mechatronic Engineering.
    ENGLISH 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.