Optimization Of Cationic Liposome Formulations For Use In Vivo

Much research has been directed toward the synthesis of new cationic lipids. Some new formulations led to the discovery of more efficient transfection agents for cells in culture. However, their efficiency measured in vitro did not correlate with their ability to deliver DNA after administration in animals. Functional properties defined in vitro do not assess the stability of the complexes in plasma or their pharmacokinetics and biodistribution, all of which are essential for optimal activity in vivo. Colloidal properties of the complexes in addition to the physicochemical properties of their component lipids also determine these parameters. In particular, in addition to efficient transfection of target cells, nucleic acid-liposome complexes must be able to traverse tight barriers in vivo and penetrate throughout the target tissue to produce efficacy for the treatment of disease. These are not issues for achieving efficient transfection of cells in culture with the exception of polarized tissue culture cells. Therefore, we are not surprised that optimized liposomal delivery vehicles for use in vivo may be different than those used for efficient delivery to cells in culture.

In summary, in vivo nucleic acid-liposome complexes that produce efficacy in animal models of disease have extended half-life in the circulation, are stable in serum, have broad biodistribution, efficiently encapsulate various sizes of nucleic acids, are targetable to specific organs and cell types, penetrate across tight barriers in several organs, penetrate evenly throughout the target tissue, are optimized for nucleic acid : lipid ratio and colloidal suspension in vivo, can be size fractionated to produce a totally homogenous population of complexes prior to injection, and can be repeatedly administered. Recently, we demonstrated efficacy of a robust liposomal delivery system in small and large animal models for lung (15), breast (17), head and neck (Hung and Templeton, 2002), and pancreatic cancers (16), and for hepatitis B and C (Clawson and Templeton, 2000). Based on efficacy in these animal studies, this liposomal delivery system will be used in upcoming clinical trials to treat these cancers. Our studies demonstrated broad efficacy in the use of liposomes to treat disease and have dispelled several myths that exist concerning the use of liposomal systems.

10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

Get My Free Ebook

Post a comment