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Dexamethasone and Dexamethasone Phosphate: Effect on DMPC Membrane Models.

Candelaria Ines Cámara1,2, Matías Ariel Crosio3,4, Ana Valeria Juarez1,2

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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.

Keywords:
DexamethasoneDexamethasone phosphatedimyiristoylphophatidylcholinemembrane models

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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.