Stimuli-Responsive Microgel-Based Materials and Their Assembly for Controlled Drug Delivery and Sensing Systems

Abstract

Conventional drug delivery methods result in a burst of drug concentration in plasma, followed by a decline, which leads to issues with maintaining drug concentrations in the therapeutic range. Furthermore, this high plasma concentration can lead to undesirable (and dangerous) side effects that minimizes patient compliance with such treatments. As a result, novel controlled drug delivery systems are being developed that can maintain the drug within the desired therapeutic range for longer times with a single dose, leading to enhanced clinical outcomes. Drug delivery systems that respond to endogenous or exogenous cues inherently present in living systems, provides possibilities to develop novel drug delivery and tissue engineering strategies. This thesis covers the general scope of stimuli-responsive polymers on a basis of temperature-responsive poly (N-isopropylacrylamide) (pNIPAm) microgels, their co-functional polymers, their assemblies and their applications in controlled/triggered drug delivery and sensing systems, which can solve problems related to human health and the environment. Firstly, I give a brief introduction of stimuli-responsive polymers, their assemblies and applications, and also discusses background of controlled drug delivery especially for smart drug delivery systems (Chapter 1). After that, we fabricated microgel-based stretchable reservoir devices for elongation enhanced small molecule release rate. Such release rate could be tuned by varying the Au layer thickness coating the microgels and device elongation. Importantly, the release process of small molecules could be turned on/off simply by stretching and relaxing the etalons (Chapter 2). Futhermore, by tuning the chemistry of microgels, we were able to develop novel temperature/light-responsive poly(N-isopropylacrylamide-co-nitrobenzyl methacrylate) (pNIPAm-co-NBMA) microgels for the use of delivering a model drug (fluorescein). Moreover, we proved that either UV irradiation or heat can promote the on-demand release of preloaded drug into the aqueous solution (Chapter 3). On the basis of such novel temperature/light-responsive microgels, we described the study of utilizing pNIPAm-co-NBMA microgels in the field of controlled osteogenic differentiation of human mesenchymal stem cells (hMSCs). Dexamethasone (DEX), a synthetic glucocorticoid, has been found to be the earliest and more readily small molecule osteogenic inducers for hMSCs, which can be loaded into pNIPAm-co-NBMA microgels, and released in a light-controlled manner. Such DEX-loaded photo-responsive microgels were able to control hMSCs osteogenic differentiation upon light exposure (Chapter 4). Subsequently, since chitosan is an attractive non-toxic, biocompatible and biodegradable polymer, we tried to develop a system of doxorubicin-hydrochloride (Dox-HCl) encapsulated chitosan-based supramolecular nanogels for the use of pH and ATP competitive drug release (Chapter 5). Moreover, pNIPAm-based sensing system related to human health have also attracted more attention to date. An optical sensor assembled by poly(N-isopropylacrylamide) (pNIPAm)-microgels for analysis of volatile organic compounds (VOC) such as hexane, cyclohexane, chloroform, petroleum ether and tetrahydrofuran (THF) were fabricated. The sensitivity, selectivity, response time and limit of detection of our sensors are investigated in details (Chapter 6). In Chapter 7, conclusion and future outlook are expressed to discuss. Ultimately, the appendix A and B have been included in the end of this dissertation, which consists of preliminary experimental results on related research projects during my Ph.D. program.