Design, Synthesis, and Evaluation of Biodegradable Polymeric Nano-Carriers for Biomedical Applications

Abstract

Biodegradable polymers have attracted significant attention in the recent years because of their important biomedical applications in tissue engineering, drug delivery, gene delivery, and various biomedical devices. In tissue engineering field, combined with cells and bioactive factors, biodegradable polymers are employed as the scaffold to guide cell migration, proliferation and differentiation, thereby enabling the regeneration of injured tissues or the development of functional tissues-like structures for replacement of diseased organs. Significant progress has been achieved in the design of biodegradable scaffolds, benefiting from the advances in chemistry and biology. Thus, scaffolds that can be degraded by biological stimuli, such as enzymes, pH, and redox activity, are being developed for applications requiring local degradability of the biomaterials. Alternatively, other types of the scaffolds that can be degraded by light have been emerged for remote spatiotemporal control of degradability. In situ modulation of biochemical and biophysical properties of the scaffolds can be achieved by appropriate degradation of the scaffolds spatially and temporally. This allows studying the cell behavior in real time, and provides deeper understanding on the complex interdependent cellular signals. On-demand control over degradability has also enabled regulation of stem cells fate, and change of their differentiation commitments during culture. Development of biodegradable carriers for the delivery of chemotherapeutic cargos to tumor cells is also an intriguing area of research. Drug delivery systems aim to localize the chemotherapeutics in the tumor tissues, thus increasing their antitumor efficacy. This provides potential solutions to the drawbacks associated with chemotherapy through direct administration, such as non-specificity, low bioavailability, cytotoxicity to health tissues, and poor solubility. Well-defined biodegradable polymeric carriers in the form of micelles, dendrimers, polymersomes, and polymer-drug conjugates enable permit physical encapsulation or chemical conjugation of anticancer drugs, and the resulting drug-loaded formulations are promising candidates for cancer treatment. Considerable efforts in drug delivery systems are currently focusing in the development of biodegradable nanocarriers for systemic delivery of antitumor drugs, which can bypass the physiological barriers of different tumor tissues. Researchers are also devoting their efforts to development of biodegradable injectable hydrogels as local depots for remote on-demand release of drugs using either chemical or physical stimuli, which is in addition to the fabrication of biodegradable patches for local delivery through skin. Furthermore, increasing attention has also been given to the design of biodegradable carriers for drug and gene co-delivery. This approach has demonstrated improved antitumor efficacy as compared to individual delivery systems. This thesis focuses on the development of biodegradable polymeric biomaterials with tunable physicochemical properties for biomedical applications. Specifically, well-defined polymer-based biomaterials are synthesized for tissue engineering, drug delivery, and drug and gene co-delivery.