Engineering nanostructured polysaccharide-based polyelectrolyte complexes

The overall goal of this dissertation is to demonstrate how the structure and composition of polysaccharide-based materials might be tuned at the nanometer length scale.;The polysaccharides used in this work were chitosan, heparin, and hyaluronan. These three polysaccharides are biodegradable, biocompatible, and non-toxic. This work demonstrates the ability to tune the structure and composition of polysaccharide assemblies at the nanoscale by controlling the conditions under which the polyelectrolytes are complexed.;The formation of PEMs using these polylelectrolytes was studied via in situ Fourier-transform surface plasmon resonance (FT-SPR). Multilayer assembly was characterized as a function of both pH and ionic strength of buffer both with in situ and ex situ techniques. Both chitosan-heparin and chitosan-hyaluronan multilayers were electrostatically deposited on a gold surfaces for up to ten layers. X-ray photoelectron spectroscopy (XPS) and polarization-modulation infra-red reflection absorption spectroscopy (PM-IRRAS) were used to characterize the chemistry and composition of the multilayer thin films.;The physical properties of chitosan, heparin, and hyaluronan in solution at different pH and ionic strength of buffer were also characterized and discussed in this work. The conformation in solution for these three polyelectrolytes was studied using gel permeation chromatography. Molecular weight distribution, hydrodynamic radius, Mark-Houwink parameters, and intrinsic viscosity were measured for each macromolecule.;The formation of PCNs using these three polyelectrolytes was also investigated in this work. PCNs have shown promising potential for the stabilization and delivery of several therapeutic agents, and have also been used in tissue engineering studies. A procedure was developed to form nanoparticles using chitosan, heparin, and hyaluronan. PCNs were complexed by combining polyelectrolyte solutions at different charge mixing ratios to promote the complexation of oppositely charged polyelectrolytes in solution. The size distributions and compositions of PCNs can be altered by changing the charge mixing ratios of the two constituent polyelectrolytes. Positively charged PCNs contain chitosan in excess, and negatively charged PCNs have either heparin or hyaluronan in excess. Formation of PCNs was best accomplished by one-shot addition of polyelectrolytes in pH 5.0, 0.1 M buffer. The variations in PCN size, zeta potential, and morphology with charge mixing ratio were studied for both positively charged and negatively charged PCNs made from each of the two polyelectrolyte combinations.;Finally, this work describes how PCNs can be combined with PEMs by electrostatically adsorbing PCNs during PEM deposition. The topography and composition of these polysaccharide-based, PCN-containing, PEM surface coatings can be tuned at the nanoscale. PCNs were adsorbed to oppositely charged PEMs, and were also embedded within PEMs. Nanostructured surface coatings were characterized on both modified gold substrates and tissue-culture polystyrene surfaces. The formation of these surface coatings was monitored by in situ quartz crystal microbalance with dissipation experiments. Surface topography was characterized by scanning electron microscopy and atomic force microscopy. Surface chemistry was confirmed by both PM-IRRAS and XPS. We demonstrate that PEM thickness can be controlled with nanometer resolution by altering the deposition conditions (buffer pH, molarity, number of layers). We demonstrate that PCNs were colloidally stable and homogeneously distributed when adsorbed on or in the PEMs. The combination of PCNs and PEMs can be used to tune the nanoscale topographical features and composition of polysaccharide-based ultra thin films. (Abstract shortened by UMI.)...