Molecular interactions in imatinib-DPPC liposomes

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Imatinib (Gleevec®) is a novel chemotherapeutic agent against Bcr-Abl protein tyrozine kinase, playing a crucial role in the therapy of chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST). Our study aimed at designing a liposomal imatinib formulation and investigating molecular interactions between lipid and imatinib, within the liposomal membrane. Multilamellar (MLV) and small unilamellar (SUV) vesicles were prepared from α-l-dipalmitoyl-phosphatidylcholine (DPPC). The effect of imatinib on the DPPC membrane was studied by electron paramagnetic resonance (EPR) spectroscopy and differential scanning calorimetry (DSC), at pH 5.2 and 9.0, where imatinib is in monocationic and neutral form, respectively. Our results indicate that imatinib interacts mainly with the DPPC head groups, leading to a slight increase in the mobility of the polar headgroups in case of MLVs. Contrary to that, imatinib causes a significant decrease in the fluidity of SUVs, which can be the result of a pH-dependent fusion/fission effect. The size distribution and morphology of liposomes were checked by dynamic light scattering and freeze-fracture electron microscopy. Our results direct attention to investigate the interactions of imatinib with artificial/biological membranes.

Original languageEnglish
Pages (from-to)205-211
Number of pages7
JournalEuropean Journal of Pharmaceutical Sciences
Volume27
Issue number2-3
DOIs
Publication statusPublished - Feb 2006

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1,2-Dipalmitoylphosphatidylcholine
Liposomes
Artificial Membranes
Imatinib Mesylate
Unilamellar Liposomes
Gastrointestinal Stromal Tumors
Membranes
Differential Scanning Calorimetry
Electron Spin Resonance Spectroscopy
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Protein Kinases
Spectrum Analysis
Electron Microscopy
Lipids

Keywords

  • DPPC
  • EPR
  • Freeze-fracture TEM
  • Gleevec
  • SUV

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Molecular interactions in imatinib-DPPC liposomes. / Béni, S.; Budai, M.; Noszál, B.; Gróf, P.

In: European Journal of Pharmaceutical Sciences, Vol. 27, No. 2-3, 02.2006, p. 205-211.

Research output: Contribution to journalArticle

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