| dc.description.abstract | There is an ever-increasing desire to develop novel materials that could control the
release of active compounds and increase their stability. Replacing petroleum-based synthetic polymers with sustainable materials has many advantages, such as reducing the
dependence on fossil fuels, and diminishing environmental pollution. Recently, cellulose
nanocrystal (CNC) obtained by acid hydrolysis of cellulose fibres has gained a lot of interest.
The high mechanical strength, large and negatively charged surface area, and the
presence of several hydroxyl groups that allow for modification with different functionalities
make CNC an excellent candidate for various applications in the biomedical field. This
thesis explores (i) the surface modification and characterization of modified CNC and (ii)
the biomedical applications of these novel sustainable nanomaterials.
In the first part, amine functionalized CNC was prepared. Ammonium hydroxide was
reacted with epichlorohydrin (EPH) to produce 2-hydroxy-3-chloro propylamine (HCPA),
which was then grafted to CNC using an etherification reaction. A series of reactions were
carried out to determine the optimal conditions. The final product (CNC-NH2(T)) was
dialyzed for one week. Further purification via centrifugation yielded the sediment (CNC-NH2(P)) and supernatant (POLY-NH2). The presence of amine groups was confirmed by
FT-IR and the amine content was determined by potentiometric titration and elemental
analysis. A high amine content of 2.2 and 0.6 mmol amine/g was achieved for CNC-NH2(T) and CNC-NH2(P), respectively. Zeta potential measurements confirmed the charge
reversal of amine CNC from negative to positive when the pH was decreased from 10
to 3. TEM images showed similar structural properties of the nanocrystals along with
some minor aggregation. This simple, yet effective synthesis method can be used for
further conjugation as required for various biomedical applications. Moreover, the surface
of CNC was modified with chitosan oligosaccharide (CSos). First, the primary alcohol
groups of CNC were selectively oxidized to carboxyl groups using the catalyst, 2,2,6,6-
tetramethylpiperidine-1-oxyl radical (TEMPO), and were then reacted with the amino
groups of CSos via the carbodiimide reaction using N-hydroxysuccinimide (NHS) and
1-Ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC). The appearance of C=O peak
in FT-IR spectrum of oxidized CNC (CNC-OX), accompanied by calculations based on
potentiometric titration revealed that CNC was successfully oxidized with a degree of
oxidation of 0.28. The grafting of CSos on oxidized CNC was confirmed by the following
observations: (i) the reduction of the C=O peak in FT-IR of CNC-CSos and the appearance
of new amide peaks; (ii) the significant reduction of the carbonyl peak at 175 ppm in the
13C NMR spectrum for CNC-CSos; (iii) a higher decomposition temperature in TGA of
CNC-CSos; (iv) a positive zeta potential of CNC-CSos at acidic pH; and (v) a degree of substitution of 0.26, which is close to the DO (0.28), indicating that 90% of COOH
groups on CNC-OX were involved in the formation of amide bonds with CSos. TEM and
AFM studies also revealed a completely diff erent morphology for CNC-CSos.
In the second part, the potential of exploiting CNCs as delivery carriers for two cationic
model drugs, procaine hydrochloride (PrHy) and imipramine hydrochloride (IMI), were
investigated. IMI displayed a higher binding to CNC derivatives compared to PrHy.
Isothermal titration calorimetry (ITC), transmittance and zeta potential measurements
were used to elucidate the complexation between model drugs and CNC samples. It was
observed that the more dominant exothermic peak observed in the ITC isotherms leading
to the formation of larger particle-drug complexes could explain the increased binding
of IMI to CNC samples. Drug selective membranes were prepared for each model drug
that displayed adequate stability and rapid responses. Different in vitro release profiles
at varying pH conditions were observed due to the pH responsive properties of the systems. Both drugs were released rapidly from CNC samples due to the ion-exchange e ffect, and CNC-CSos displayed a more sustained release profile. Furthermore, the antioxidant properties of CNC samples and the potential of CNC-CSos as a carrier for the delivery of vitamin C was investigated. CNC-CSos/vitamin C complexes (CNCS/VC) were formed between CNC-CSos and vitamin C via ionic complexation using sodium tripolyphosphate (TPP). The complexation was confirmed via DSC and UV-Vis absorbance measurements.
TEM images showed complexes with a size of approximately 1 micron. The encapsulation
efficiency of vitamin C was higher (91%) at pH 5 compared to pH 3 (72%). The in
vitro release of vitamin C from CNCS/VC complexes exhibited a sustained release of up
to 3 weeks, with the released vitamin C displaying higher stability compared to a control
vitamin C solution. Antioxidant activity and kinetics of various CNC samples were studied
using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. CNC-CSos possessed a higher
scavenging activity and faster antioxidant activity compared to its precursors, CNC-OX
and CSos, and their physical mixture. Therefore, by loading vitamin C into CNC-CSos
particles, a dynamic antioxidant system was produced. Vitamin C can be released over a
prolonged time period displaying enhanced and sustained antioxidant properties since the
carrier CNC-CSos also possesses antioxidant properties.
As a result of this doctoral study, knowledge on the surface modification of CNC with
amine groups and CSos have been advanced. The in vitro drug release and antioxidant
studies suggest that systems comprising of CNC could be further explored as potential
carriers in biomedical applications. | en |
