Characterization of molecular dynamics and elastic properties of flexible liposomes membranes using Fast-Field-Cycling NMR

MARÍA BELÉN MARZOLA CORONEL; CARLA CECILIA FRAENZA; ESTEBAN ANOARDO

Congreso; EUROMAR2017; 2017

At present, the development of nanometric vesicles for drug delivery in the human body by different routes has become of great interest for the pharmaceutical industry. Flexible liposomes have proved to be useful for transdermal transport, therefore it is important to measure the bending elastic modulus k of the membrane. This constant has an inverse proportionality relation with the parameter called deformability or adaptability of the vesicles, being one of the most relevant parameters related to the penetration dynamics in the skin. In previous works [1-4], a model was presented to interpret the spin-lattice relaxation rate dispersion of protons, obtained with the fast field cycling nuclear magnetic relaxometry technique (FFC), for unilamellar liposomes. In addition to providing general information on the lipid dynamics, this model allows us to infer about the elastic properties of the liposomes by means of the elastic constant k , which is one of the physical parameters involved in the model. This model has been validated from measurements of k for cholesterol doped vesicles in order to increase thevalue of the constant. On the other hand, in order to extend it in the opposite limit of membrane flexibility, experiments using elastic vesicles were performed in this work. Specifically, we analyzed experimental relaxation dispersions obtained at different temperatures (291-328K) for liposomes of radius of 50nm, composed of SPC (soy phosphatidylcholine) with different ionic (sodium deoxycholate) and nonionic (Tween 80 and BrijO20) detergents added to enhance the membrane flexibility, at concentrations up to 40 mol%. The model was successfully extended for this type of liposomes. Variations in k were moderate (around 40%) in response to the additive concentration up to 20mol%. However, we observed some particular changes in the way diffusion and order fluctuations affect the proton spin-lattice relaxation as detergent concentration is increased, for the three used detergents.[1] C. J. Meledandri, J. Perlo, E. Farrher, D. F. Brougham, E. Anoardo, Interpretation of Molecular Dynamics on Different Time Scales in Unilamellar Vesicles Using Field-Cycling NMR Relaxometry. J. Phys. Chem. B 113: 15532-15540, 2009.[2] J. Perlo, C. J. Meledandri, E. Anoardo, D. F. Brougham Temperature and Size-Dependence of Membrane Molecular Dynamics in Unilamellar Vesicles by Fast Field-Cycling NMR Relaxometry. J. Phys. Chem. B 115: 3444-3451, 2011.[3] C. C. Fraenza, C. J. Meledandri, E. Anoardo, D. F. Brougham, The Effect of Cholesterol on Membrane Dynamics on Different Timescales in Lipid Bilayers from Fast Field‐Cycling NMR Relaxometry Studies of Unilamellar Vesicles. ChemPhysChem 15: 425-435, 2014.[4]- G. A. Domingez, J. Perlo, C. C. Fraenza and E. Anoardo, Measurement of the Bending Elastic Modulus in Unilamellar Vesicles Membranes by FastField Cycling NMR Relaxometry. Chem. Phys. Lipids 201: 21-27, 2016.