Recombination of Nanometric Vesicles during Freeze-Drying

Concentrated dispersions of nanometric lipid vesicles (mean diameter 20 nm) in water/maltose solutions have been freeze-dried and then redispersed in water, yielding again dispersions of lipid vesicles. At each stage of the freeze-drying process, the organization of the vesicles in the dispersion and their size distribution were examined through small-angle neutron scattering and gel permeation chromatography. It was found that the osmotic deswelling of the vesicles caused them to recombine into larger vesicles. A single burst of recombination events occurred when the maltose concentration in the aqueous phase rose above 100 g/L. The final vesicle population was monopopulated, with a central diameter about twice as large as that of the original dispersion.