Physical study of the arrangement of pure catanionic glycolipids and interaction with phospholipids, in support of the optimisation of anti-HIV therapies

Abstract

In a first part, the comprehension of the antiviral efficiency of a Gemini catanionic analogue of GalCer Gem16-12-16 is deepened by studying its interactions with phospholipids. Monolayers at the air/water interface are used as 2D models of biological membrane. Adsorption kinetics measurements are performed at Gemini concentrations below the critical aggregation concentration (CAC) and show an incorporation of Gem16-12-16 molecules into the fluid phase as well as into the condensed domains of a DPPC monolayer. Compressing such a mixed monolayer leads first to the squeezing out of Gem16-12-16 molecules from the fluid part of the monolayer and above 30 mN/m to the squeezing out from the condensed part. SAXS/WAXS studies are performed using mixtures of Gem16-12-16 catanionic surfactant and DPPC. Bilayers have been observed at high concentrations for Gem16-12-16 in water, in a large temperature range. Mixing with DPPC produces mixed bilayers above the corresponding chain melting temperature. At room temperature, partially lamellar aggregates with local nematic order are observed. In a second part, the ability to encapsulate anti-HIV drugs of another analogue of GalCer Tri16-12-12 is studied. A difference in monolayer stability of pure Tri16-12-12 is observed on water or on buffer subphases, encouraging us to perform the first encapsulation assays in buffer solutions. First results on a fluorescent probe entrapment inside the vesicles are performed in order to validate the use of these vectors in anti-HIV therapy.