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

Eva Horn Moeller, Birgitte Holst, Line Hagner Nielsen, Pia Steen Pedersen, Jesper Østergaard

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

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: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. (C) 2009 Elsevier B.V. All rights reserved.
Original languageEnglish
JournalInternational Journal of Pharmaceutics
Volume390
Issue number1
Pages (from-to)13-18
Number of pages6
ISSN0378-5173
DOIs
Publication statusPublished - 2010
Externally publishedYes

Keywords

  • Animals
  • Calorimetry, Differential Scanning
  • Cholesterol
  • Drug Stability
  • Electrophoresis, Capillary
  • Ghrelin
  • Liposomes
  • Male
  • Particle Size
  • Phospholipids
  • Rats
  • Rats, Sprague-Dawley
  • Static Electricity
  • Transition Temperature
  • 97C5T2UQ7J Cholesterol
  • buffer
  • cholesterol
  • dipalmitoylphosphatidylcholine
  • dipalmitoylphosphatidylserine
  • ghrelin
  • glycerophospholipid
  • liposome
  • phosphatidylcholine
  • thioflavine
  • unclassified drug
  • animal experiment
  • appetite
  • article
  • capillary electrophoresis
  • chemical interaction
  • controlled study
  • differential scanning calorimetry
  • drug absorption
  • drug blood level
  • drug formulation
  • drug stability
  • high performance liquid chromatography
  • in vivo study
  • light scattering
  • male
  • nonhuman
  • phase transition
  • priority journal
  • rat
  • suspension
  • turbidity
  • zeta potential
  • Delivery
  • In vivo
  • Liposome
  • Liposome interaction
  • Prolonged effect
  • PHARMACOLOGY
  • CAPILLARY-ELECTROPHORESIS
  • GROWTH-HORMONE
  • SUBCUTANEOUS INJECTION
  • UNILAMELLAR VESICLES
  • INTRAVENOUS GHRELIN
  • APPETITE REGULATION
  • BINDING CONSTANTS
  • RAT GHRELIN
  • FOOD-INTAKE
  • INSULIN
  • cholesterol 57-88-5
  • dipalmitoylphosphatidylcholine 2644-64-6
  • dipalmitoylphosphatidylserine 3036-82-6
  • ghrelin 304853-26-7 hormone-drug pharmacokinetics, subcutaneous administration
  • 10060, Biochemistry studies - General
  • 10066, Biochemistry studies - Lipids
  • 10067, Biochemistry studies - Sterols and steroids
  • 12512, Pathology - Therapy
  • 22002, Pharmacology - General
  • 22016, Pharmacology - Endocrine system
  • Pharmacology
  • affinity capillary electrophoresis electrophoretic techniques, laboratory techniques
  • differential scanning calorimetry laboratory techniques, spectrum analysis techniques
  • Biochemistry and Molecular Biophysics
  • Methods and Techniques
  • Pharmaceuticals

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