Characterisation of the Self-Assemblies Properties and Interaction with Models Membranes of New Type of Amphiphilic Cyclodextrins : A DLS and SS-NMR Study

Abstract

Thanks to their abilities to form inclusion complexes and nanoparticles with many hydrophobic drugs, cyclodextrins are widely used for vectorization(1). Nevertheless, the poor diffusion of these systems through cell membrane and the low stability of their aggregates remain major obstacles, particularly for pharmaceutical applications(2). To deal with this problem, amphiphilic cyclodextrins are commonly used in the literature(3). This work presents the characterization of the nanoparticles obtained by the aggregation of new types of amphiphilic cyclodextrins(4), lipophosphoramidyl-cyclodextrins and glycerolipidyl-cyclodextrins, as well as the study of their influences on model membranes. Dynamic Light Scattering (DLS) shows that the nanoparticles have a diameter lower than 400nm and stability greater than 14 days. Amphiphilic cyclodextrin/lipid interactions have been studied by 31P and 2H Solid-State NMR (SS-NMR) on multilamellar vesicles (MLV) with different composition used to mimic cell membranes. 31P NMR experiment shows a global insertion of amphiphilic cyclodextrins and 2H NMR data suggest disturbance of the lipid dynamics due to cyclodextrins, which seems to be influenced by the nature of the lipid chains. Indeed, in the case of MLV of DMPC (C14:0), a rigidification has been observed whereas an increase of the lipid dynamics is noted for liposomes constituted by POPC (18:1; 16:0). Finally, results obtained on a third model, POPC-d31/CH/SM (5.2/3.3/1.5), which contains cholesterol and sphingomyelin, two major lipid class found in natural plasma membrane, show also a fluidification.Reference:(1)S. V. Kurkov. & T. Loftsson, International Journal of Pharmaceutics, (2013), 453, 167-180.(2)H. Parrot-Lopez et al., Annales Pharmaceutiques Francaises, (2010), 68, 12-26.(3)V. Bonnet et al., Drug Discovery Today, (2015), 20(9), 1120-1126.(4)C. Gervaise et al., Biochimie, (2012), 94, 66-74.