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Stability, liposome interaction, and in vivo pharmacology of ghrelin in liposomal suspensions. | LitMetric
Ghrelin is an appetite-stimulating peptide hormone. It is a pharmacologically interesting peptide because of its involvement in e.g. appetite and metabolism, but it has a very short half-life in the body. Ghrelin carries a Ser-3-octanoyl group, and it has previously been suggested that acylated peptides can bind to or be incorporated into liposomes. Therefore, neutral dipalmitoylphosphatidylcholine (DPPC) liposomes and phosphatidylcholine:cholesterol (PC:Chol) (70:30) liposomes as well as negatively charged dipalmitoylphosphatidylcholine:dipalmitoylphosphatidylserine (DPPC:DPPS) liposomes (70:30) were prepared, and ghrelin was added. The chemical and physical stability of ghrelin was examined. Affinity capillary electrophoresis (ACE) revealed an interaction between ghrelin and the negatively charged (DPPC:DPPS) liposomes, whereas only very small affinities were discerned in the other liposomal formulations of ghrelin. Differential scanning calorimetry showed no changes in phase transitions (T(m)). In vivo pharmacokinetics following subcutaneous administration of ghrelin in buffer and in the liposomal formulations was examined in rats. The PC:Chol formulation had a longer-lasting effect as compared to the ghrelin buffer solution and the other two liposomal formulations. The prolonged effect of the PC:Chol formulation is suggested not to be caused by association between ghrelin and the liposome.
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