title: Characterization of thermosensitive chitosan-based hydrogels by rheology and electron paramagnetic resonance spectroscopy.
abstract: Chitosan, an amino-polysaccharide, has been proposed as a promising biopolymer for tissue repair and drug delivery. Chitosan solutions containing glycerol-2-phosphate (beta-GP) have been described as injectable in situ gelling thermosensitive formulations, which undergo sol-gel transition at physiological pH and temperatures. This feature makes them suitable for the parenteral administration of drugs, especially for peptides and proteins. The aim of the present study was to get a deeper insight into the macro- and microstructure of chitosan/beta-GP systems. In addition to oscillating rheology, electron paramagnetic resonance (EPR) spectroscopy was applied to examine the microviscosity and pH inside the gels depending on the beta-GP concentration and to follow the loading and release of spin-labelled Insulin. All chitosan/beta-GP solutions showed a physiological pH ranging from 6.6 to 6.8 that did not change during gelation, irrespective of the proportion of beta-GP. The dynamics of the spin-labelled Insulin and its microviscosity inside the gels and during release were monitored by EPR spectroscopy. The results indicate that the Insulin was incorporated into the aqueous environment of the gel and was released in its native form. The in vitro drug release from the gels was governed by diffusion of drug from the gel matrix. A sustained release of Insulin was observed over a period of 2 weeks. Increasing the proportion of beta-GP increased the amount of released Insulin and the velocity thereof.
authors.affiliation: Martin-Luther-University Halle-Wittenberg, Institute of Pharmaceutics and Biopharmaceutics, Wolfgang-Langenbeck-Strasse 4, Halle/Saale, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Kempe
authors.forename: Hendrik
authors.initials: H
authors.lastname: Metz
authors.forename: Martin
authors.initials: M
authors.lastname: Bastrop
authors.forename: Annette
authors.initials: A
authors.lastname: Hvilsom
authors.forename: Renata Vidor
authors.initials: RV
authors.lastname: Contri
authors.forename: Karsten
authors.initials: K
authors.lastname: Mäder
mesh_terms: D048271:Chitosan / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004058:Diffusion; D004337:Drug Carriers / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D005782:Gels / Q000737:chemistry; D005994:Glycerophosphates / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007267:Injections; D007328:Insulin / Q000737:chemistry*; D012212:Rheology; D013696:Temperature; D014783:Viscosity
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005782:Gels; D005994:Glycerophosphates; D020100:Hydrogels; D007328:Insulin; D048271:Chitosan; C031463:beta-glycerophosphoric acid