Organic electronic biomaterials for bioelectronic regenerative medicine

Ashton, Mark and Hardy, John (2021) Organic electronic biomaterials for bioelectronic regenerative medicine. PhD thesis, Lancaster University.

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Abstract

The use of stimuli responsive materials in drug delivery systems is an established field in modern medicine, potentially providing a non-invasive way of delivering controlled amounts of drug with spatial and temporal control to specific tissues. Photo-responsive and electro-responsive drug delivery systems are interesting because of their ability to affect drug release non-invasively, which may improve patient compliance during long term treatments. Current leading drug delivery systems (e.g. oral and topical) are limited in their use by their release profiles and patient compliance. The work presented herein attempts to address these issues through the development of biodegradable and biocompatible stimuli responsive drug delivery systems. Synthesis of a range of poly(caprolactone)-based electro-responsive polymers are reported here demonstrating the ability to process them in solution (potentially enabling processing into a variety of materials morphologies, exemplified in this thesis by films). The polymers were shown to release a consistent amount of drug with temporal control when stimulated with electricity. The cytocompatibility and biodegradability of these compounds was demonstrated and attributed to the composition of the polymer backbones (composed of poly(caprolactone) and porphyrins) and are predicted to affect a minimal immune response during long term implantation. The ability to tailor release profiles based on the extent of conjugation of the electroactive component of the polymer was successfully demonstrated. In order to explore this approach further a range of oligomeric units with increased conjugation were successfully synthesised and incorporated into polymers. These polymers were shown to exhibit higher release profiles in line with their extended conjugation. Photo stimulated release was also demonstrated from the same films generating a range of release profiles by switching between the two stimuli. The photodegradation pathway can be utilised to affect breakdown of the film post drug release. This film breakdown mechanism should diminish prospects for surgical removal of the implanted film post release reducing the potential impact on the patient and diminishing the financial burden on the health system. The oligomeric and monomer units in these studies have been shown to generate highly biocompatible and biodegradable polymers that can be processed into mechanically stable films suitable for extended implantation. These polymers may enable spatial control of drug delivery by selecting the site of implantation and non-invasive irradiation with light. An alternative approach is through the utilisation of polymer assemblies in solution as drug delivery systems. Analogous poly(ethylene glycol)-based polymer vesicles have shown the structural characteristics to target inflamed/cancerous tissues due to the enhanced permeation and retention effect consequently we investigated controlled release from assemblies of these new polymers and demonstrate their potential for spatial and temporal control. This project encompasses a range of novel materials utilising different delivery methods to enable drug delivery in response to electricity and light stimuli. A range of polymers have demonstrated the ability to consistently release controlled amounts of doped/encapsulated drugs in response to an external stimulus. We anticipate these polymers will perform well in-vivo and be successful in delivering drugs in response to a stimuli and thereby improve patient compliance, which will be the subject of future studies.