Dexamethasone and Dexamethasone Phosphate: effect on DMPC membrane models.

C.I.CAMARA; CROSIO, M; JUAREZ, ANA; N. WILKE,

Congreso; L Reunión Anual SAB; 2022

INTRODUCTION: 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.OBJETIVE: Study the adsorption of Dex and Dex-P on DMPC membranes models (LUVs, GUVs, monolayers). Understand how the presence of the drugs in a hybrid monolayer modifies the interfacial film properties of DMPC. Characterize the effect over cellular bilayer of a high doses of the drug when is applied locally.CONCLUSIONSDex partially mixes with DMPC in Langmuir monolayer, making the monolayer more compressible, avowing the LE/LC phase transition of DMPC after a molar fraction of 0.5 and inducing a decrease in reflectivity in the pressure range of 35-50mN/m. On the contrary Dex-P just widens the range of pressures in which the LE/LC phases coexists, without any modification in Rp and kapp. Dex and Dex-P presence induce the appearance of aggregates at all molar fraction. The number of aggregates increase with the increment in surface pressure and drug molar fraction. The average size of the aggregates is around 5-7µm2 and 6-12µm2 for Dex and Dex-P respectively and slightly higher for Dex-P at molar fraction lower than 0.8. Rp values of aggregates are higher than the corresponding to the LC phase of DMPC but not enough to be a DMPC bilayer. With all these evidence it very probable that the aggregate correspond to Dex or Dex-P segregation. Dex-P adsorb in DMPC vesicles, decreasing the z-potential (vesicle more negative). When Dex-P adsorb on GUVs the percent of fluctuating GUVs decrease as consequence of the increase of electrostatic repulsion (the membrane bending is more energetically expensive).