|Ph.D Student||Eliyahu Shaked|
|Subject||Nanometric Mucoadhesive Carriers for Macromolecule|
|Department||Department of Nanoscience and Nanotechnology||Supervisor||PROF. Havazelet Bianco-Peled|
|Full Thesis text|
The ability to adhere to mucosal surfaces, termed mucoadhesion, is considered valuable for pharmaceutical purposes, as mucosal drug delivery has great potential to provide improved drug absorption and bioavailability. Drug residence time on mucosal surfaces can be prolonged using polymers designed to attach to mucosal membranes. Such mucoadhesives are a useful tool for mucosal drug delivery. Polymeric nanoparticulate mucoadhesive carriers have even greater potential, because they can adhere to mucosal tissues and offer increased surface area enhancing the bioavailability by protecting the drug from degradation.
This thesis is composed of two projects. The first aimed to investigate the effect of acrylate modification on the mucoadhesion of chitosan at the nanoscale. A second goal was to investigate the effect of cryoprotection and freeze-drying on the physical and chemical properties of the nanoparticles and explore the potential of these carriers to deliver drugs. Nanoparticles were fabricated from acrylated chitosan (ACS) via ionic gelation with tripolyphosphate and were characterized in terms of size, zeta potential and stability. Chitosan (CS) nanoparticles, serving as a control, were fabricated using the same procedure. The mucoadhesion of the nanoparticles was evaluated using the flow-through method after different incubation periods. The retention of ACS nanoparticles was found to be significantly higher compared with CS nanoparticles. Cryoprotection was achieved using sucrose and revealed that ACS nanoparticles are less sensitive to freeze-drying in terms of size. The incorporation of a macromolecular drug increased the nanoparticle size and decreased the zeta potential for both fresh and freeze-dried formulations. In addition, the freeze-dried nanoparticles presented penetration across a mucus gel layer and the flow through technique revealed that short term mucoadhesive properties were not impaired. ACS nanoparticles were able to deliver a model drug across a mucin gel layer but could not improve drug penetration through the triple co-culture cell model that was used in order to mimic the small intestine epithelium.
The second project focused on examining a new hydrogel system based on the physical and chemical interactions of pectin modified with thiol groups and chitosan modified with acrylate end groups. Gelation occurred at high pectin thiol ratios, indicating that a low acrylated chitosan concentration in the hydrogel had a profound effect on the cross-linking. Turbidity, Fourier transform infrared spectroscopy, and free thiol determination analyses were performed to determine the relationships of the different bonds inside the gel. At low pH values below the pKa of chitosan, more electrostatic interactions were formed between opposite charges, but at high pH values, the Michael-type addition reaction between acrylate and thiol took place, creating harder hydrogels. Swelling experiments and Young’s modulus measurements were performed to study the structure and properties of the hydrogels. The nanostructure was examined using small-angle X-ray scattering. Texture profile analysis showed a unique property of hydrogel adhesiveness. By implementing changes in the preparation procedure, we controlled the hydrogel properties. This hybrid hydrogel system can be a good candidate for a wide range of biomedical applications, such as a mucosal biomimetic surface for mucoadhesive testing.