Encapsulation and Diffusion of Water-Soluble Dendrimers in a Bicontinuous Cubic Phase

Bicontinuous cubic (Q II ) phases composed of hydrated lipids are a unique mesoporous organic material. The diameter of the water channels in the range of 5−10 nm could be used as a reservoir for macromolecular therapeutic agents. Here, we describe the synthesis of water-soluble poly(amidoamine) (PAMAM) dendrimer derivatives labeled with fluorine and their diffusion in the water channels of a Q II phase. A Q II phase with Ia 3 d symmetry was prepared by hydration of a 9:1 molar mixture of polymerizable monoacylglycerol and the corresponding 1,2-diacylglycerol. The dendrimers having fluorine were synthesized by Michael reaction of PAMAM dendrimers with a mixture of ethyl 4,4,4-trifluorocrotonate and methyl acrylate. The hydrated diameter of the fluorinated dendrimer of generation 2.5 (G2.5AFH) is 32.6 Å as measured by 19 F NMR. The diffusion coefficient of G2.5AFH at 25 °C in the water channels of the Q II phase, determined by pulsed field gradient 19 F NMR spectroscopy, is 1 × 10 - 12 m 2 /s, which is compared to the free diffusion coefficient of the dendrimer in water (1.42 × 10 - 10 m 2 /s). These data indicate that small globular proteins or similar molecules can diffuse rapidly enough in stabilized Q II phases to be technically useful.