Factors influencing the enhanced hypocalcemic action of liposome-entrapped calcitonin.

The mechanism whereby liposomal entrapment enhances the hypocalcemic effect of calcitonin (CT) was evaluated in the rat. Phosphatidylcholine (PC) and PC plus cholesterol (PCC) preparations of large multilammelar vesicles (MLV) and small unilammelar vesicles (SUV) were used to entrap human calcitonin (hCT). The effect of each of these preparations was assessed by measuring plasma calcium after their parenteral administration. Changes in calcium were compared with plasma concentrations of liposomal hCT (L-hCT) and free hCT (F-CT). The plasma form of hCT was also evaluated by gel filtration chromatography. Most of the liposomal preparations had a greater hypocalcemic effect than unencapsulated hCT. Following I.V. administration, the MLV-hCT preparations had the greatest hypocalcemic effect. Thus, to enhance the hypocalcemic effect of hCT, large vesicular size is important for I.V. administration and the absence of cholesterol in the liposome is important for I.M. administration. In general, the greatest hypocalcemic effect was achieved by those liposomal preparations that resulted in the most sustained increase of L-hCT and F-hCT in plasma. Thus, liposomal entrapment enhances the hypocalcemic effect of hCT by prolonging the presence of the peptide in the peripheral circulation.