Stability, liposome interaction, and in vivo pharmacology of ghrelin in liposomal suspensions

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 pept...

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Bibliographic Details
Published in:International journal of pharmaceutics 2010-05, Vol.390 (1), p.13-18
Main Authors: Moeller, Eva Horn, Holst, Birgitte, Nielsen, Line Hagner, Pedersen, Pia Steen, Østergaard, Jesper
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Calorimetry, Differential Scanning
Cholesterol - chemistry
Delivery
Drug Stability
Electrophoresis, Capillary
General pharmacology
Ghrelin
Ghrelin - administration & dosage
Ghrelin - chemistry
Ghrelin - pharmacokinetics
In vivo
Liposome
Liposome interaction
Liposomes - chemical synthesis
Liposomes - chemistry
Male
Medical sciences
Particle Size
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Phospholipids - chemistry
Prolonged effect
Rats
Rats, Sprague-Dawley
Static Electricity
Transition Temperature
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Summary: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.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2009.05.067