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Oral delivery of vancomycin by tetraether lipid liposomes.
Journal article

Oral delivery of vancomycin by tetraether lipid liposomes.

  • Uhl P Department of Nuclear Medicine, Ruprecht-Karls University, University Hospital, 69120 Heidelberg, Germany.
  • Pantze S Institute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls University, 69210 Heidelberg, Germany.
  • Storck P Department of Nuclear Medicine, Ruprecht-Karls University, University Hospital, 69120 Heidelberg, Germany.
  • Parmentier J Institute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls University, 69210 Heidelberg, Germany.
  • Witzigmann D Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
  • Hofhaus G Bioquant, CellNetWorks, University of Heidelberg, Heidelberg, Germany.
  • Huwyler J Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
  • Mier W Department of Nuclear Medicine, Ruprecht-Karls University, University Hospital, 69120 Heidelberg, Germany.
  • Fricker G Institute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls University, 69210 Heidelberg, Germany.. Electronic address: gert.fricker@uni-hd.de.
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  • 2017-07-19
Published in:
  • European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. - 2017
Liposome
Oral bioavailability
Tetraether lipids
Vancomycin
Administration, Oral
Animals
Anti-Bacterial Agents
Biological Availability
Caco-2 Cells
Cell Survival
Chemistry, Pharmaceutical
Diglycerides
Drug Delivery Systems
Drug Stability
Ethers
Glycolipids
Humans
Lipids
Liposomes
Male
Nanoparticles
Particle Size
Rats
Rats, Wistar
Vancomycin
English Despite the outstanding progress in modern medicine, the oral delivery of peptide drugs is limited until today due to their instability in the gastrointestinal tract and low mucosa penetration. To overcome these hurdles, liposomes containing the specific tetraether lipid GCTE (glycerylcaldityltetraether lipid) were examined. For this purpose, the glycopeptide antibiotic vancomycin was used as model substance and liposomes were prepared by DAC (dual assymetric centrifugation). These liposomes showed a size and polydispersity index comparable to standard liposomes. A high encapsulation efficiency of 58.53±1.76% of the peptide drug vancomycin could be obtained as detected by HPLC. FCS analysis showed that in average each liposome contains 30 molecules of vancomycin. TEM and Cryo-EM micrographs verified the size and lamellarity of the liposomal formulations. Cytotoxicity tests in Caco-2 cells showed no significant cytotoxicity for all liposomal concentrations tested, indicating the good tolerability of these formulations. Furthermore, the use of sucrose as lyoprotector enabled the long term storage of the liposomal formulation for at least three months. The potency of this drug delivery system could be proven in an animal model using Wistar rats. One hour after oral application, 4.82±0.56% of the administered dose of vancomycin could be found in the blood as detected by immunoassay measurements. This transport did also not affect the integrity of the peptide as verified by immunoassay measurements. In combination with long term storage stability, this formulation appears to be a promising delivery system for oral application of peptide drugs.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/17870
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