Nanoparticles are vastly studied drug delivery systems aiming at altering or improving the pharmacokinetics and pharmacodynamics of both low and high molecular weight drugs. Among the different materials used in the preparation of nanoparticulate drug delivery systems, polysaccharides offer several benefits, such as versatility, biodegradability and biocompatibility. Nanoparticles based on polysaccharides are thus promising drug delivery systems. In the formulation of new drug delivery systems, the understanding of the mechanisms and parameters affecting their properties is essential. The considerations summarized above laid the grounds for this thesis with the overall aim of investigating parameters that could affect the preparation and physicochemical characteristics of nanoparticles based on the polysaccharides chitosan and pectin for potential applications in drug delivery. The main results obtained are reported in four papers that cover the development of a method for the estimation of the nanoparticle compactness, the preparation and characterization of nanoparticles based on chitosan or pectin, and the colloidal stability of the nanoparticles. Moreover, initial studies on the potential mucoadhesive properties of selected chitosan and pectin based nanoparticles are reported in this thesis summary.
The results presented demonstrate that both chitosan and pectin nanoparticles could be prepared by ionotropic gelation in the presence of sodium chloride, while chitosan microparticles and a macroscopic pectin network were formed in the absence of sodium chloride. The nanoparticle characteristics could easily be adjusted by changing the solvent salinity, the type and concentration of polysaccharide, and the crosslinker to polysaccharide ratio applied in the particle preparation. The main differences between the chitosan and the pectin nanoparticles were their positive and negative charge, respectively, and that the chitosan nanoparticles were generally smaller and more compact than the pectin nanoparticles. Both the chitosan and the pectin nanoparticles studied were mainly found to be colloidally stable after one week of storage. The chitosan nanoparticles interacted more strongly with mucin than the pectin nanoparticles in vitro, indicating a stronger ability to adhere to the body’s protective mucus gel layer. The findings in this thesis offer a decent platform for further studies on the applicability of polysaccharide based nanoparticles for drug delivery applications.
List of papers
(II-IV are removed due to publisher restrictions)
I H. Jonassen, A.-L. Kjøniksen. Optical-scattering method for the determination of the local polymer concentration inside nanoparticles. Physical Review E 84, 022401 (2011) DOI: 10.1103/PhysRevE.84.022401
II H. Jonassen, A.-L. Kjøniksen, M. Hiorth. Effects of ionic strength on the size and compactness of chitosan nanoparticles. Colloid and Polymer Science 290, 919-929 (2012) DOI: 10.1007/s00396-012-2604-3
III H. Jonassen, A.-L. Kjøniksen, M. Hiorth. Stability of chitosan nanoparticles cross-linked with tripolyphosphate. Biomacromolecules 13, 3747-3756 (2012) DOI: 10.1021/bm301207a
IV H. Jonassen, A. Treves, A.-L. Kjøniksen, G. Smistad, M. Hiorth. Preparation of ionically cross-linked pectin nanoparticles in the presence of chlorides of divalent and monovalent cations. Biomacromolecules 14, 3523–3531 (2013) DOI: 10.1021/bm4008474