A non-covalently cross-linked chitosan based hydrogel.

Abstract

Hydrogels are normally formed by the covalent cross-linking of linear polymers. In the case of chitosan based hydrogels this cross-linking is often achieved with glutaraldehyde, glyoxal or other reactive cross-linking agents. Such hydrogel materials have limited biocompatibility and biodegradability. However by the attachment of hydrophobic palmitoyl groups to glycol chitosan, a water soluble chitosan derivative, we have produced a version of the amphiphilic vesicle forming polymer-palmitoyl glycol chitosan (Uchegbu et al., 1998, J Pharm Pharmacol 58, 453-458). The level of palmitoylation in this variant of the polymer (GCP11), as determined by proton neutron magnetic resonance spectroscopy, is 19.62+/-2.42% (n=4). GCP11 has been used to prepare soft, slowly eroding hydrogels suitable for drug delivery by simply freeze-drying an aqueous dispersion of the polymer. Non-covalent cross-linking to form the gel matrix is achieved by the hydrophobic interactions of the palmitoyl groups. The resulting material, as examined by scanning electron microscopy, is porous and may be hydrated to up to 20x its weight in aqueous media without any appreciable change in volume-transforming from an opaque to a translucent solid. The slow erosion of this material in aqueous environments gives a biodegradable and ultimately more biocompatible material than covalently cross-linked hydrogels. Unlike most chitosan-based gels, the gel is hydrated to 20x its weight at alkaline pH but only 10x its weight at neutral and acid pH. This is as a result of the gradual erosion of the gel at lower pH values. Hydration is also reduced from 20x the dry gel weight in water to 10x the dry gel weight in the presence of dissolved salts such as sodium chloride. GCP11 hydrogels have been loaded to 0.1% w/w with a model fluorophore, rhodamine B, by simply freeze-drying an aqueous dispersion of GCP11 in the presence of a solution of rhodamine B dissolved in either water or phosphate buffered saline (PBS, pH=7.4). The release of this model fluorophore was retarded by between 8 and 12% when PBS was contained in the gel in accordance with the hydration profiles. Rhodamine B release was also reduced by between 13 and 25% in the presence of acid as a result of the reduced solubility of rhodamine B at acid pH.