Dexamethasone and Dexamethasone Phosphate: Effect on DMPC Membrane Models
Candelaria Ines Cámara1,2, Matías Ariel Crosio3,4, Ana Valeria Juarez1,2
1Departamento de Fisicoquímica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba X5000HUA, Argentina.
Pharmaceutics
|March 29, 2023
Summary
Dexamethasone (Dex) and Dexamethasone phosphate (Dex-P) interact with cell membranes. Dex alters membrane properties more than Dex-P, with both drugs penetrating lipid bilayers.
Area of Science:
- Biochemistry
- Physical Chemistry
- Pharmacology
Background:
- Dexamethasone (Dex) and Dexamethasone phosphate (Dex-P) are potent synthetic glucocorticoids used for their anti-inflammatory and immunosuppressive effects.
- Their critical role in reducing mortality in severe COVID-19 patients highlights the importance of understanding their interaction with biological membranes.
Purpose of the Study:
- To investigate the effects of Dex and Dex-P on dimyristoylphosphatidylcholine (DMPC) membranes.
- To elucidate the distinct interaction mechanisms of Dex and Dex-P with lipid bilayers.
Main Methods:
- Utilized Langmuir films and vesicles to study drug-membrane interactions.
- Employed surface pressure measurements, reflectivity analysis, and vesicle shape fluctuation analysis.
Main Results:
- Dex incorporation into DMPC monolayers increased compressibility, reduced reflectivity, induced aggregates, and suppressed the LE/LC phase transition.
- Dex-P also formed aggregates but did not disrupt the LE/LC phase transition or reflectivity.
- Dex exhibited greater surface pressure changes than Dex-P due to higher hydrophobicity, with both drugs penetrating membranes at high lipid packing.
Conclusions:
- Both Dex and Dex-P can penetrate and modify the mechanical properties of DMPC membranes.
- Dex-P adsorption to giant unilamellar vesicles (GUVs) of DMPC reduced membrane deformability.
