Encapsulation of bilayer vesicles by self-assembly

Vesicles of lipid bilayers have been investigated as drug-delivery vehicles for almost 20 years(1-8). The vesicles' interior space is separated from the surrounding solution because small molecules have only limited permeability through the bilayer. Single-walled (unilamellar) vesicles are made by a variety of non-equilibrium techniques, including mechanical disruption of lamellar phases by sonication or extrusion through filters, or chemical disruption by detergent dialysis or solvent removal(5). These techniques do not, however, allow the encapsulation of a specific volume, nor can they be used to encapsulate other vesicles. Here we show that molecular-recognition processes mediated by lipophilic receptors and substrates (here the biotin-streptavidin complex)(9) can be used to produce a multicompartmental aggregate of tethered vesicles encapsulated within a large bilayer vesicle. We call these encapsulated aggregates vesosomes. Encapsulation is achieved by unrolling bilayers from cochleate clyinders(5,10-12) which are tethered to the aggregate by biotin-streptavidin coupling. These compartmentalized vesosomes could provide vehicles for multicomponent or multifunctional drug delivery(2-4,6); in particular the encapsulating membrane could significantly modify permeation properties, or could be used to enhance the biocompatibility of the system.