Liposomes Within a Lipsome.
A Novel Extended-Release Delivery Vehicle
Cecile Boyer
Department of Chemical Engineering
UCSB Doctoral Candidate
Date:
Tuesday, February 8, 2005
Time: 4:00 p.m.
Place: Engineering II, Room 3361
ABSTRACT
An efficient drug delivery vehicle should have a high loading capacity with minimal toxicity, exhibit high retention and stability, and deliver its contents at a specific target site. Our proposed delivery system consists of loaded liposomes, encapsulated within another bilayer: the liposome membrane provides a way to sequester drugs in defined spaces, while the outer bilayer is found to have a protective effect. In addition, the different membranes can be decorated with a variety of agents to fulfill the requirements for an efficient carrier .
We have developed a simple method to encapsulate loaded liposomes within another bilayer via a combination of self-assembly and directed assembly of a variety of saturated phospholipids. We routinely obtain encapsulation efficiencies of 96% after repeated sedimentation. When higher purity is required, a negative selection process based on magnetic labeling can be used to remove essentially all remaining free liposomes. The unencapsulated material may be recovered, concentrated and recycled into other encapsulation processes. This technology can be applied to liposomes loaded with a wide variety of compounds, including CarboxyFluorescein and Sucrose. For weak bases, such as the antibiotic Ciprofloxacin, active loading can be used to greatly increase the amount of intraliposomal material.
The retention properties of our liposome-within-a-liposome system were characterized in the presence of a variety of biologically relevant agents such as Phospholipase A 2 , an enzyme which hydrolyzes the building blocks of the liposomes. To better approximate the complex conditions encountered in the body, further release studies were performed in serum. In all cases, our new system vastly outperforms single membrane liposomes. We have thus created and characterized an efficient new extended-release delivery vehicle.