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Interactions between aminoglycosides and phospholipids using liposomes: a possible mechanism of nephrotoxicity
1Tokyo College of Pharmacy, Japan.
Abstract:
Interactions of aminoglycosides with phospholipids were estimated by the increase in turbidity of liposomes consisting of various phospholipids. The turbidity of liposomes containing negatively charged phospholipids was increased by gentamicin, the highest increase in turbidity being observed for phosphatidylinositol-4,5-diphosphate-containing liposomes. The extent of turbidity was dependent on the concentration of acidic phospholipid in the liposomal membrane as well as the number of amino groups of the aminoglycosides. The release of glucose from glucose-entrapped liposomes depended on the concentration of gentamicin. The turbidity of liposomes containing lipids extracted from rat renal cortex was also increased by aminoglycosides depending on the number of amino groups. From electron microscopic observations, the increase in turbidity of liposome suspensions was caused by liposome fusion.
Insights
Aminoglycoside antibiotics interact with negatively charged phospholipids in liposomes, causing liposome fusion. This interaction, particularly with phosphatidylinositol-4,5-diphosphate, is concentration-dependent and affects glucose release.
Area of Science:
- Biochemistry
- Pharmacology
- Lipid Bilayer Studies
Background:
- Aminoglycosides are antibiotics known for potential nephrotoxicity.
- Understanding their interaction with cellular membranes is crucial for predicting toxicity and efficacy.
- Phospholipids form the structural basis of cell membranes.
Purpose of the Study:
- To investigate the interaction between aminoglycoside antibiotics and various phospholipids.
- To elucidate the mechanism behind aminoglycoside-induced changes in liposome structure.
- To correlate these interactions with potential membrane disruption and drug release.
Main Methods:
- Liposomes composed of different phospholipids were prepared.
- Turbidity measurements were used to quantify liposome aggregation and fusion.
- Electron microscopy visualized structural changes in liposomes.
- Glucose release assays assessed membrane permeability changes.
Main Results:
- Gentamicin increased liposome turbidity, especially with negatively charged phospholipids like phosphatidylinositol-4,5-diphosphate.
- Turbidity increase correlated with acidic phospholipid concentration and aminoglycoside amino group number.
- Gentamicin concentration influenced glucose release from liposomes.
- Electron microscopy confirmed liposome fusion as the cause of increased turbidity.
Conclusions:
- Aminoglycosides interact strongly with negatively charged phospholipids, leading to liposome fusion.
- The extent of interaction is dependent on both the lipid composition and the aminoglycoside structure.
- These findings provide insights into the membrane interactions of aminoglycosides, potentially explaining cellular uptake or toxicity mechanisms.