Chemical and Biomolecular Engineering - Theses
Permanent URI for this collection
Search Results
1 - 1 of 1
-
ItemMultifunctional, covalently stabilised capsules from biodegradable materials( 2010)One of the most promising and fast-developing areas of nanotechnology is the design of carrier systems for biomedical applications. These particulate delivery vehicles can be engineered with highly defined properties with a range of sizes, shapes and functionalities. Polymeric nanocapsules assembled using the Layer-by-Layer (LbL) technique are widely regarded as promising candidates for the delivery of biologically relevant agents. By choosing to use naturally occurring polyelectrolyte as LbL materials, such as poly(L-Lysine) (PLL) and poly(L-glutamic acid) (PGA, the resulting capsules can be degraded using enzymes that are present in certain environments within the body. In order to produce covalently stabilised multilayer films, PLL and PGA were modified with alkyne and azide moieties, respectively, enabling the formation of a covalent triazole bond between adjoining layers in the presence of copper during LbL assembly (click chemistry reaction). Stable one-component films and capsules were prepared and characterised. Properties such as enzymatic degradation, tuneable pH-responsive swelling, cytotoxicity, permeability and protein adhesion to the capsule surface were investigated. PLL click films were also equipped with targeting moieties as a proof of concept. The concept of stratified LbL assembly was introduced to tailor the degradation kinetics of the biodegradable hybrid capsules. To investigate drug loading, polymer-drug conjugates of PGA and anticancer drugs (doxorubicin or paclitaxel) were synthesised. The modular LbL assembly approach allowed for loading of these conjugates to multilayer films. A high level of control over drug position and dose was achieved and drugs could subsequently be release by enzymatic degradation. The uptake to colorectal cancer cells and the effect of drug-loaded capsules on cell viability was also investigated. In addition, a drug-resistant cell line was established and the capsular delivery method of anticancer-drugs was found to restore sensitivity of the drug-resistant cell line towards these drugs. In a different approach, PGA was modified with dopamine for continuous assembly of biodegradable capsules with defined properties. Overall, this thesis suggests various promising approaches for the assembly of biodegradable, multifunctional and covalently-stabilised capsules with potential application in targeted drug delivery.