ENCAPSULATION OF BILAYER VESICLES BY SELF-ASSEMBLY

Vesicles of lipid bilayers have been investigated as drug-delivery veh icles for almost 20 years(1-8). The vesicles' interior space is separa ted from the surrounding solution because small molecules have only li mited permeability through the bilayer. Single-walled (unilamellar) ve sicles are made by a variety of non-equilibrium techniques, including mechanical disruption of lamellar phases by sonication or extrusion th rough 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 vesic les. Here we show that molecular-recognition processes mediated by lip ophilic 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 e ncapsulated aggregates vesosomes. Encapsulation is achieved by unrolli ng bilayers from cochleate clyinders(5,10-12) which are tethered to th e aggregate by biotin-streptavidin coupling. These compartmentalized v esosomes could provide vehicles for multicomponent or multifunctional drug delivery(2-4,6); in particular the encapsulating membrane could s ignificantly modify permeation properties, or could be used to enhance the biocompatibility of the system.