Screening for the drug-phospholipid interaction: correlation to phospholipidosis

Juha-Matti Alakoskela, Pavol Vitovic, Paavo K J Kinnunen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Phospholipid bilayers represent a complex, anisotropic environment fundamentally different from bulk oil or octanol, for instance. Even "simple" drug association to phospholipid bilayers can only be fully understood if the slab-of-hydrocarbon approach is abandoned and the complex, anisotropic properties of lipid bilayers reflecting the chemical structures and organization of the constituent phospholipids are considered. The interactions of drugs with phospholipids are important in various processes, such as drug absorption, tissue distribution, and subcellular distribution. In addition, drug-lipid interactions may lead to changes in lipid-dependent protein activities, and further, to functional and morphological changes in cells, a prominent example being the phospholipidosis (PLD) induced by cationic amphiphilic drugs. Herein we briefly review drug-lipid interactions in general and the significance of these interactions in PLD in particular. We also focus on a potential causal connection between drug-induced PLD and steatohepatitis, which is induced by some cationic amphiphilic drugs.
Original languageEnglish
JournalChemMedChem
Volume4
Issue number8
Pages (from-to)1224-51
Number of pages27
ISSN1860-7179
DOIs
Publication statusPublished - 1. Aug 2009

Fingerprint

Drug Interactions
Phospholipids
Screening
Pharmaceutical Preparations
Lipids
Octanols
Lipid Bilayers
Fatty Liver
Hydrocarbons
Oils
Lipid bilayers
Tissue
Proteins

Keywords

  • Cell Membrane Permeability
  • Drug Evaluation, Preclinical
  • Humans
  • Lipid Bilayers
  • Lipidoses
  • Lysosomes
  • Pharmaceutical Preparations
  • Phospholipids

Cite this

Alakoskela, Juha-Matti ; Vitovic, Pavol ; Kinnunen, Paavo K J. / Screening for the drug-phospholipid interaction: correlation to phospholipidosis. In: ChemMedChem. 2009 ; Vol. 4, No. 8. pp. 1224-51.
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Screening for the drug-phospholipid interaction: correlation to phospholipidosis. / Alakoskela, Juha-Matti; Vitovic, Pavol; Kinnunen, Paavo K J.

In: ChemMedChem, Vol. 4, No. 8, 01.08.2009, p. 1224-51.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Screening for the drug-phospholipid interaction: correlation to phospholipidosis

AU - Alakoskela, Juha-Matti

AU - Vitovic, Pavol

AU - Kinnunen, Paavo K J

PY - 2009/8/1

Y1 - 2009/8/1

N2 - Phospholipid bilayers represent a complex, anisotropic environment fundamentally different from bulk oil or octanol, for instance. Even "simple" drug association to phospholipid bilayers can only be fully understood if the slab-of-hydrocarbon approach is abandoned and the complex, anisotropic properties of lipid bilayers reflecting the chemical structures and organization of the constituent phospholipids are considered. The interactions of drugs with phospholipids are important in various processes, such as drug absorption, tissue distribution, and subcellular distribution. In addition, drug-lipid interactions may lead to changes in lipid-dependent protein activities, and further, to functional and morphological changes in cells, a prominent example being the phospholipidosis (PLD) induced by cationic amphiphilic drugs. Herein we briefly review drug-lipid interactions in general and the significance of these interactions in PLD in particular. We also focus on a potential causal connection between drug-induced PLD and steatohepatitis, which is induced by some cationic amphiphilic drugs.

AB - Phospholipid bilayers represent a complex, anisotropic environment fundamentally different from bulk oil or octanol, for instance. Even "simple" drug association to phospholipid bilayers can only be fully understood if the slab-of-hydrocarbon approach is abandoned and the complex, anisotropic properties of lipid bilayers reflecting the chemical structures and organization of the constituent phospholipids are considered. The interactions of drugs with phospholipids are important in various processes, such as drug absorption, tissue distribution, and subcellular distribution. In addition, drug-lipid interactions may lead to changes in lipid-dependent protein activities, and further, to functional and morphological changes in cells, a prominent example being the phospholipidosis (PLD) induced by cationic amphiphilic drugs. Herein we briefly review drug-lipid interactions in general and the significance of these interactions in PLD in particular. We also focus on a potential causal connection between drug-induced PLD and steatohepatitis, which is induced by some cationic amphiphilic drugs.

KW - Cell Membrane Permeability

KW - Drug Evaluation, Preclinical

KW - Humans

KW - Lipid Bilayers

KW - Lipidoses

KW - Lysosomes

KW - Pharmaceutical Preparations

KW - Phospholipids

U2 - 10.1002/cmdc.200900052

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M3 - Journal article

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