Design and Optimisation of Polymer Nanoparticles for Advanced Healthcare Applications

Abstract

The World Health Organisation has highlighted widening health inequalities and increased pressure on healthcare systems as major global health challenges. Key contributors to these disparities are uneven distribution of specialised instruments in centralised laboratories and expensive pharmaceuticals in resource-limited settings, resulting in delayed disease diagnosis and treatment. This emphasises the urgent need for developing low-cost, robust point-of-care (PoC) sensors and affordable, effective and precision targeted pharmaceuticals. To address these issues and reduce the healthcare inequalities, this thesis aims to develop polymer-based solutions that are suitable for both diagnostics and pharmaceuticals. This thesis is organised into seven chapters. The extensive literature review of different polymers for the sensors/therapeutics is given in chapter 1. Chapter 2 details the chemicals/monomers used to prepare the polymers/polymeric nanoparticles and methodologies employed for sensing and drug delivery application. The design and optimisation of electroactive molecularly imprinted polymeric nanoparticles (nanoMIPs) as recognition element for PoC electrochemical glucose sensor (chapter 3). The glucose detection is demonstrated in both diabetic patient serum samples and in artificial interstitial fluids indicating its potential for wearable technology applications. The protein imprinting is crucial for separation and detection of the range of proteins. Therefore, chapter 4 explores the synthesis of full protein lysozyme (major allergic protein in eggs) imprinted nanoMIPs and optimising them for developing lysozyme impedimetric/thermal sensors. Given the intriguing application of imprinted polymers in drug delivery, chapter 5 is dedicated to developing targeted drug nanocarriers using double imprinting approach for breast cancer treatment. The drug delivery of hydrophobic silymarin drug is investigated using mixed Pluronics micelles (commercial surface-active polymers) in chapters 6. Different mixed micellar formulations are studied for their effect on solubilisation of silymarin. Further different solubilisation methods and drug loading capacities of various polymeric micelles are investigated for the delivery of two poorly water-soluble nutraceuticals (naringenin and baicalein) in chapter 7. This thesis demonstrates the diverse applications of imprinted and surface-active polymers for diagnostic and drug delivery, offering more robust and cost-effective solutions to overcome the healthcare inequalities.