Three-dimensional liposome networks: Freeze fracture electron microscopical evaluation of their structure and in vitro analysis of release of hydrophilic markers

This paper summarises first experiences with highly concentrated, semisolid phospholipid dispersions. Their preparation is based on 'forced hydration' of (phospho-)lipid(s) by high-pressure homogenisation in the presence of relatively low amounts of water. The inner structure of the obtained semisolid pastes, as revealed by freeze-fracture electron microscopy, is best described as a matrix of densely packed vesicles. Depending on the lipid content the characteristics of these vesicles range from very homogeneous, small and unilamellar to more heterogeneous in size as well as lamellarity. Although not comparable to 'classical' liposome dispersions these multivesicular pastes may be useful as drug carriers. Results from in-vitro release tests demonstrate that they may serve as local depots for controlled release of active compounds. Two release mechanisms are observed occurring at the same time: (1) release of free active molecules via diffusion out of the matrix and (2) budding off of active compound-carrying liposomes from the matrix. Release type and rate are determined among other factors by the phospholipid content of the matrices and thus by their inner structure.