ABSTRACT
A novel injectable in situ gelling thermosensitive chitosan-beta-glycerophosphate (C-GP) formulation has been recently proposed for tissue repair and drug delivery. The system can sustain the release of macromolecules over a period of several hours to a few days. However, with low-molecular-weight hydrophilic compounds, the release is generally completed within 24 h. In this study, liposomes were added to the C-GP solution and their effect on the viscoelastic properties of the system and release kinetics of encapsulated carboxyfluorescein was investigated. The gelation rate and gel strength were slightly increased by the presence of the liposomes. The in vitro release profiles demonstrated controlled delivery over at least 2 weeks. The release rate strongly depended on the liposome size and composition (i.e. addition of cholesterol), and on the presence of phospholipase in the release medium. The kinetics was not substantially modified when using liposomes prepared with a negatively-charged lipid or a lipid having a high phase transition temperature. These results indicate that the liposome-C-GP system rapidly gels at body temperature, and can sustain the delivery of low-molecular-weight hydrophilic compounds. A mathematical model was proposed to characterize the release kinetics.
Subject(s)
Biocompatible Materials/chemistry , Chitin/analogs & derivatives , Chitin/chemistry , Glycerophosphates/chemistry , Hydrogels/chemistry , Chitosan , Drug Carriers/chemistry , Fluoresceins/chemistry , Kinetics , Liposomes , Microscopy, Electron , Models, Theoretical , Molecular Weight , Rheology , Solutions , Thermodynamics , ViscosityABSTRACT
The aim of this study was to investigate the physical properties of a chitosan/glycerophosphate (GP) thermosensitive solution which gels at 37 degrees C and evaluate the in vitro release profiles of different model compounds. The gelation rate was dependent on the temperature and on the chitosan deacetylation degree. The solution containing 84%-deacetylated chitosan could be stored 3 months at 4 degrees C without apparent change in viscosity. The in vitro release profiles of the model compounds depended on the presence of GP in the chitosan solution, on their molecular weight and on the presence of lysozyme in the release media. They were not affected by the electrostatic charge of the model compound when present at low concentrations. During the first 4 h, the release was accompanied by a substantial loss of the gel weight which was mainly attributed to the leaching of water and excess GP. Scanning electron micrographs revealed that the solutions yield gels with a highly porous structure after 24 h of exposure to a continuous flow of phosphate buffered saline. These results indicate that the chitosan/GP thermosensitive solutions gel rapidly at body temperature, can remain in the sol state at 4 degrees C and can sustain the delivery of macromolecules.
