CHARACTERIZATION, STABILITY AND IN-VIVO TARGETING OF LIPOSOMAL FORMULATIONS CONTAINING CYCLOSPORINE

Cyclosporin A (CSA) is a potent immunosuppressive drug that was recent ly encapsulated into different liposomal formulations. Optimization of CSA formulated liposomes preparation was the goal of this study. Lipo somes composed of dipalmitylphosphatidylcholine (DPPC) containing CSA were prepared and characterized by differential scanning calorimetry ( DSC). In vitro characterization of the formulated model liposomes incl uding the entrapment efficiency and stability in the presence of mono- and divalent ions at different temperatures (5, 21, 37 degrees C) and in the absence and presence of cholesterol (Chol) was carried out. Fu rthermore, in vivo targeting of CSA to mouse livers from liposomal pre parations was investigated and compared with a non-liposomal formulati on. A slight decrease in transition temperature (T-m) of the liposomes formed was noted with increase in CSA content. Entrapment of CSA in t he liposomal vesicles was found to be dependent to some extent on the Chol level. The release rate of CSA from liposomes was enhanced in the presence of the divalent ions, Ca2+ and Mg2+, indicating low stabilit y in the presence of these ions compared with Na+. The release rate wa s affected by storage temperature and depended on the existence of Cho l. In the absence of Chol, the release rate decreased with increasing temperature. On the other hand, in the presence of Chol, the rate of r elease was directly proportional to the temperature. In vivo study sho wed that a higher CSA content which lasted for more than 11 days was a chieved in mouse livers from liposomal compared with non-liposomal pre parations.