Dexamethasone and Dexamethasone Phosphate: effect on DMPC membrane models.

CAMARA, CANDELARIA INES; CROSIO, MATIAS; JUAREZ, VALERIA ANA; WILKE, NATALIA

Rosario, Santa Fe

Congreso; L Reunión Anual SAB; 2022

Asociación Argentina de Biofísica (SAB)

Dexamethasone (Dex) and Dexamethasone phosphate (Dex-P) are syntheticsglucocorticoids with a high anti-inflammatory and immunosuppressive action. Recently,its action has gained visibility because it reduces the mortality in critical patients withCOVID-19 connected to assisted breathing. Both drugs have been widely used for thetreatment of several disease, including chronical treatments. For this reason, is importantunderstand the behavior of Dex and Dex-P in presence of membranes models, the firstbarrier when the drug get into the body.The variation of dimyiristoylphophatidylcholine (DMPC) monolayer and bilayer propertiesas Dex and Dex-P inserted into the film in different molar proportions were studied usingLangmuir isotherm, Brewster angle microscopy, insertion experiments and vesiclefluctuation analysis.Our result indicates that Dex makes DMPC hybrid monolayer more compressible inducinga decreasing reflectivity in the pressure range of 35-50mN/m. At molar fraction biggerthan 0.5, suppress the Liquid Expanded /Liquid Condensed (LE/LC) phase transition ofDMPC. At the same time, Dex presence induce the appearance of aggregates at any molarfraction. The number of aggregates increase with the increment in Dex molar fraction.Otherwise, Dex-P presence also induce the aggregates formation in DMPC/Dex-P hybridfilm without disturbing the LE/LC phase transition and reflectivity in any range ofpressure. Insertion experiments demonstrate that Dex induce bigger change in surfacepressure than Dex-P, due to it higher hydrophobic character. The exclusion pressure forDex and Dex-P were 36 and 45 mN.m-1, respectively, which indicate that both drugs canpenetrate at bigger surface pressure values than the postulated for a cellular membrane.Membrane fluctuation analysis show that Dex-P adsorption in DMPC GUVs decrease thepercent of fluctuating vesicle. In conclusion both drugs can penetrate and alter themechanical properties of DMPC membrane. Dex, due to its hydrophobic character,disrupts the lipid surface organization of DMPC, altering the nucleation process andmaking the monolayer more compressible. This effect was opposite to that observed withDex-P.