CALCITONIN-LOADED LIPOSOMES - STABILITY UNDER ACIDIC CONDITIONS AND BILE SALTS-INDUCED DISRUPTION RESULTING IN CALCITONIN-PHOSPHOLIPID COMPLEX-FORMATION

Calcitonin-loading in liposomes composed of phosphatidylcholine, chole sterol and stearylamine or dipalmitoyl phosphatidylglycerol was studie d at low pH values and in the presence of bile salts to check whether liposomal entrapment could be a possible means of protecting the pepti de against the aggressive conditions present in the gastrointestinal t ract. The association of calcitonin with the lipidic vesicles was moni tored using radioactive labelling of the peptide and gel-filtration se paration of the free and liposome-associated fractions. The results sh ow that for all phospholipid compositions tested, loading was preserve d in light acidic or basic buffers, and that only a slight disruption was observed at pH 2.5. Cholate caused a significant but only partial release of calcitonin even when the cholate-to-phospholipid ratio was increased. To understand the mode of calcitonin entrapment in the vesi cles, the release of liposome-entrapped calcein was monitored concomit antly and taken as a stability criterion. Liposome integrity appears t o be resistant at low pHs but to be totally destroyed by 4 mM cholate in a manner quasi-independent of the phospholipid concentration. These results strongly suggest that bile salts induce a disruption of the l iposomes which results in the formation of new lipidic structures invo lving calcitonin and probably cholate.