DEXAMETHASONE AND DEXAMETHASONE PHOSPHATE: EFFECT ON DMPC MEMBRANE MODELS.

C. I. CÁMARA; CROSIO, MATÍAS A.; A. V. JUAREZ; N. WILKE

Rosario

Congreso; L Reunion Anual de la sociedad Argentina de Biofísica; 2022

Sociedad Argentina de Biofísica

Dexamethasone (Dex) and Dexamethasone phosphate (Dex-P) are synthetics glucocorticoids with a high anti-inflammatory and immunosuppressive action. Recently, its action has gained visibility because it reduces the mortality in critical patients with COVID-19 connected to assisted breathing. Both drugs have been widely used for the treatment of several disease, including chronical treatments. For this reason, is important understand the behavior of Dex and Dex-P in presence of membranes models, the first barrier when the drug get into the body. The variation of dimyiristoylphophatidylcholine (DMPC) monolayer and bilayer properties as Dex and Dex-P inserted into the film in different molar proportions were studied using Langmuir isotherm, Brewster angle microscopy, insertion experiments and vesicle fluctuation analysis. Our result indicates that Dex makes DMPC hybrid monolayer more compressible inducing a decreasing reflectivity in the pressure range of 35-50mN/m. At molar fraction bigger than 0.5, suppress the Liquid Expanded /Liquid Condensed (LE/LC) phase transition of DMPC. At the same time, Dex presence induce the appearance of aggregates at any molar fraction. 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 hybrid film without disturbing the LE/LC phase transition and reflectivity in any range of pressure. Insertion experiments demonstrate that Dex induce bigger change in surface pressure than Dex-P, due to it higher hydrophobic character. The exclusion pressure for Dex and Dex-P were 36 and 45 mN.m-1, respectively, which indicate that both drugs can penetrate at bigger surface pressure values than the postulated for a cellular membrane. Membrane fluctuation analysis show that Dex-P adsorption in DMPC GUVs decrease the percent of fluctuating vesicle. In conclusion both drugs can penetrate and alter the mechanical properties of DMPC membrane. Dex, due to its hydrophobic character, disrupts the lipid surface organization of DMPC, altering the nucleation process and making the monolayer more compressible. This effect was opposite to that observed with Dex-P.