pH-responsive polymeric nanoparticles for drug delivery systems

In cancer therapy, the potential of hydrophobic drugs has been impaired by their low solubility in aqueous media. Stimuli responsive NPs have great potential for the delivery of hydrophobic drugs to a certain area in the body. Such NPs can encapsulate hydrophobic drugs, thus improving their pharmacokinetic properties while the stimuli-responsiveness can offer the controlled release of loaded drug in response to biological cues at the malignant sites. Among different stimuli, pH stands out as an interesting target to rationally design such NPs as there is drastic difference in pH has been found between healthy tissues and cancerous ones. NPs obtained from pH-responsive polymers by acidolysis reaction is an interesting class of stimuliresponsive NPs. In this thesis, different amphiphilic pH-responsive polymer has been synthesised and studied for their self-assembly in aqueous media. Following the synthesis of the amphiphilic diblock copolymer through photo-ATRP, with the hydrophilic block being PEG and the hydrophobic blocks consisting of a furan ring and a pHresponsive moiety of cyclic ketal. With the addition of a Diels-Alder adduct with the furan reacting with N-benzyl maleimide, increasing the hydrophobicity and possibility for other bonding to the drugs. The NPs had small hydrodynamic sizes form ~80nm. Dyes can be loaded also to the NPs, with a small hydrodynamic size of ~60nm. When the cyclic ketal is exposed to an acidic pH, its breaks down into a cis-diol and ketone. This forces dissociation of the NP, turning the core from hydrophobic to hydrophilic. This allows for an interesting lead on pHresponsive NPs for drug delivery systems. A synthesis of an amphiphilic random copolymer through photo-ATRP, changing the hydrophobic block to dopamine containing a catechol. These NPs hydrodynamic size between ~20nm and ~50nm although there larger NPs with unfavourable PDIs. With the addition of boronic acid to form a condensation reaction with the dopamine. However, the solubility issues lead this polymer to be less successful.

Publisher

University of Galway

Rights

Attribution-NonCommercial-NoDerivatives 4.0 International

cbn

Collections

University of Galway Theses (Research Masters Theses)