Development of a novel biomaterial for drug delivery

Gold nanoparticles (GNPs) are promising tools as drug delivery devices. However, upon intravenous injection, they aggregate and are rapidly eliminated from the systemic circulation by macrophages in the reticuloendothelial system, resulting in relatively short blood circulation time. To circumvent this problem, GNPs are typically coated with poly(ethylene) glycol (PEG). This modification significantly enhances the circulation time of the GNPs in vivo as well as the stability of the particles. However, PEG has limited possibilities of functionalization, as they only have free chemical groups available for conjugation to other molecules on their terminal ends. Alternatively, alginate-derived polymers may be good candidates as GNP stabilizing agents as they are biocompatible, have unique gel forming properties and the advantage that they can readily be conjugated to various therapeutic and targeting molecules since they contain numerous free chemical groups. In this project, a protocol for preparing thiolated alginate-derived polymers and for coating them on the surface of GNPs was established. These polymers were first characterized with analytical methods. Furthermore, physical properties of the GNPs coated with these polymers were analyzed. In vitro experiments were performed to examine the interactions between serum proteins and these GNPs, as well as the cell behavior (viability and uptake) in the presence of these GNPs. Finally, in vivo experiments were done to determine the pharmacokinetics and biodistribution of these GNPs. To verify if any toxicity was induced by the GNPs, histology studies were also done. For comparison, PEGylated and unmodified GNPs were analyzed as well. Results indicated that GNPs coated with alginate-derived polymers were uptaken by cells and had increased stability, reduced interactions with serum proteins and longer blood circulation time than unmodified GNPs. Hence, these particles pave the way for improved drug delivery systems.