470d Transport Properties of Hydrophilic and Amphiphilic Molecules in the Two Subspaces of Lipidic Cubic Phases

Yasser Qutub1, Wolfgang Donner2, Oleg Galkin1, and Peter G. Vekilov1. (1) Department of Chemical Engineering, University of Houston, 4800 Calhoun, Houston, TX 77204, (2) Department of Physics, University of Houston, 4800 Calhoun, Houston, TX 77204

Lipidic cubic phases find applications in controlled release due to their microstructure and transport properties. Determining the transport rates in lipid cubic phases is crucial to assess the notion of its applicability in sustained drug delivery. Lipidic cubic phases are also used as media for membrane protein crystallization, where protein transport plays key roles in nucleation and crystallization kinetics. Lipidic cubic phases are highly-ordered three-dimensional bicontinuous phases comprised of two interpenetrating but non-contacting aqueous compartments and a continuous curved lipidic network. At the molecular level, each subspace of the cubic phase has a characteristic viscosity—low-viscosity aqueous subspace and high-viscosity lipidic subspace. In this paper, we determine the diffusivities of an organic dye, a hydrophilic molecule, and a membrane protein, an amphiphilic molecule, in the aqueous channels and lipidic bilayer network of the cubic phase, respectively. Optical density, which is directly proportional to concentration, profiles are acquired from optical macrographs using a microscope equipped with a linear-response CCD camera. The data are fitted with the analytical solution for the unsteady-state 1-D diffusion problem in Matlab. The model computes the effective diffusion coefficient of the molecule in lipid cubic phase using nonlinear least squares fit. Our results show that the protein self-diffusivity is 1.2 x 10-8 cm2/s. This value is comparable to published results for diffusion of bR in C2E5 sponge phases and to estimates from Stokes-Einstein law of diffusion. Furthermore, we show that the protein diffusivity is inversely proportional to its concentration. This technique for diffusion determination can be used to screen various lipids or conditions to tailor the transport properties of the lipidic cubic phase for the applications discussed above, and to determine the diffusivity dependence on concentration.