Modulated release from liposomes entrapped in chitosan/gelatin hydrogels

Abstract

The paper describes the preparation of chitosan/gelatin hydrogels, obtained by double crosslinking with glutaraldehyde and sodium sulphate/sodium tripolyphosphate that may be used as matrices for the inclusion of drug loaded liposomes composed of phosphatidylcholine. The main objective was to create a protective layer to stabilize the liposomal surface and to prolong/control the release of drugs from such systems. Therefore, complex systems capable of prolonged drug release and controlled release kinetics were obtained. Samples consisting of different chitosan/gelatin ratios and type/amount of ionic crosslinker have been prepared and characterized. The present study shows that calcein (used as a model hydrophilic drug) release from polymeric hydrogels has been retarded from several days to weeks after calcein inclusion in small unilamellar vesicles (SUVs) and multilamellar vesicles (MLVs) entrapped subsequently in hydrogels with variable composition. The calcein release kinetics of complex systems were compared to simple systems (control hydrogels) and important changes were observed thus proving that the mechanism of the process increases in complexity. Also, it is demonstrated that liposomes' stability can be greatly improved by inclusion in polymeric matrices. Multilamellar liposomes showed a better release behaviour, which indicates that these calcein loaded vesicles remained intact to some extent after release from the matrix, due to their improved stability provided by the multiple layers. When small unilamellar liposomes were tested, calcein have been released from hydrogels predominantly in a free form (due to their unilamellarity related instability even inside the hydrogel) but in a sustained and controllable manner. The main applications of the systems obtained are in the area of drug release for tissue engineering/tissue repair (topical administration of drugs for wound therapy - burns, for example). Hydrogels capable of delivering drugs over prolonged periods of time represent a step forward in wound management and many diseases that request long term and sustained delivery of drugs. These hydrogels could be used as tissue replacement or injectable depot systems in many high risk diseases including cancer.

Keywords: Chitosan; Drug release mechanism; Gelatin; Hydrogels; Liposomes.