Characterization, stability and in vivo targeting of liposomal formulations containing cyclosporin

Abstract

Cyclosporin A (CSA) is a potent immunosuppressive drug that was recently encapsulated into different liposomal formulations. Optimization of CSA formulated liposomes preparation was the goal of this study. Liposomes composed of dipalmitylphosphatidylcholine (DPPC) containing CSA were prepared and characterized by differential scanning calorimetry (DSC). In vitro characterization of the formulated model liposomes including the entrapment efficiency and stability in the presence of mono- and divalent ions at different temperatures (5, 21, 37°C) and in the absence and presence of cholesterol (Chol) was carried out. Furthermore, in vivo targeting of CSA to mouse livers from liposomal preparations was investigated and compared with a non-liposomal formulation. A slight decrease in transition temperature ( T m) of the liposomes formed was noted with increase in CSA content. Entrapment of CSA in the 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, Ca 2+ and Mg 2+ indicating low stability in the presence of these ions compared with Na +. The release rate was affected by storage temperature and depended on the existence of Chol. In the absence of Chol, the release rate decreased with increasing temperature. On the other hand, in the presence of Chol, the rate of release was directly proportional to the temperature. In vivo study showed that a higher CSA content which lasted for more than 11 days was achieved in mouse livers from liposomal compared with non-liposomal preparations.