Encapsulation of vesicles and colloids via interdigitated lipid bilayers

Lipid vesicles are currently being used as drug delivery vehicles for the sustained release of a drug compound to a specific site in the body. The vesicles' interior space is separated from the surrounding solution as a result of the limited permeability of molecules through the lipid bilayer. Unilamellar vesicles can be made by a variety of techniques, however, these techniques do not allow the encapsulation of a specific volume, nor can they be used to encapsulate other vesicles. The ability to have vesicles inside of vesicles can be particularly advantageous for delivering macromolecules that are normally easily cleared in vivo. Such structures could be highly charged vesicles or positive DNA lipid complexes, both of which are normally rapidly removed after injection, but could be shielded from opsonization if encapsulated in a neutral bilayer.; This dissertation describes a novel method of encapsulation that gives a high yield of vesicle and colloidal encapsulation. These vesicles within a vesicle structures have been previously given the name “vesosomes”. In order to carry out encapsulation, interdigitated sheets were initially formed by adding ethanol to small unilamellar vesicles. The ethanol intercalates within the lipid bilayer, forcing the structures to fuse and form stable bilayer sheets. An aliquot of the colloidal particles, liposomes, or macromolecules is then mixed with the interdigitated sheets, followed by brief heating. The elevated temperature causes the interdigitated sheets to roll up and form vesicles, passively encapsulating the drug complexes in the process. We have been able to produce large-scale vesicle encapsulation with or without the use of ligand receptor binding systems. Free vesicles and vesicle aggregates have both been encapsulated efficiently, with no apparent adverse effect on the encapsulated structures. Both outer bilayer shells and the entrained vesicles can be produced from a variety of lipid mixtures, allowing for a very versatile drug delivery system. These second-generation vesosomes could provide vehicles for multi-component or multifunctional drug delivery.