Development of magnetic cationic liposomes for targeting tumor microvasculature

A popular way to attack malignant tumors is using cationic liposomes as drug delivery systems.

Their task is to target tumor vasculature while affecting as little of the healthy tissue as possible. In order to improve the targeting efficiency, Northeastern University Assistant Professor Robert B. Campbell, along with his Ph.D. student, Suman Dandamudi have been working to develop a more specific drug delivery vehicle by combining the electrostatic properties of cationic liposomes with the strength of an externally applied magnet field. Their article describing Phase I of their research, titled “Development and Characterization of Magnetic Cationic Liposomes for Targeting Tumor Microvasculature” appeared in the 2007 March issue of BBA (Biochimica et Biophysica Acta) , published by ScienceDirect.

“The ultimate goal is to get the chemotherapeutic drugs directly to the tumor blood vessels and avoid uptake by the healthy tissue,” says Robert B. Campbell, Assistant Professor of Pharmaceutical Sciences at the Northeastern's Bouve College of Health Sciences. “Cationic liposomes preferentially target tumor vessels but do accumulate in some normal healthy tissues as well. Our research suggests that attracting our cationic liposomes (containing magnetite) to the tumor vasculature with a magnet can in fact improve overall distribution in tumors and thereby limit their uptake by the healthy tissue.”

The Northeastern researchers' work builds upon his previous work conducted at Massachusetts General Hospital. Cationic liposomes were shown to target tumor vessels to a large extent over vessels in normal healthy tissues, targeting approximately 25% and 5% of the vessels, respectively. Campbell and Dandamudi intend to significantly improve the percent of injected dose that can accumulate in the tumor vascular compartment.

Their findings to date suggest that in the presence of an external magnet, magnetite-containing cationic liposomes are ideal carriers not only in terms of more accurate delivery, but for the prolonged tumor accumulation of chemotherapeutic drugs as well.

The authors point out that in addition to getting as much of the drug as possible to where it's needed, it is also important to keep it there as long as possible. “The group of mice that had magnets placed on their tumors during treatment retained the liposomes longer following removal of the magnet than did the mice without access to magnets,” Dr. Campbell explains.

Campbell and Dandamudi note that magnetic cationic liposomes are most ideal for treatment of melanoma, breast cancer and even thyroid cancer as the application of the external magnets is easier to place and more effective on the skin's surface, near the tumor.

They believe that magnetic drug targeting together with the development of novel nanotechnologies can provide additional support in the fight against cancer disease. “We must continue to develop our technologies with an understanding of our tumor targets, and not independently of them,” adds Dr. Campbell. “In light of our recent new twist on the application and use of external magnets for targeting tumor vessels, we look forward to translating our experimental findings from the laboratory setting to the clinic.”

Phase II of their research is currently underway and the developments will be available soon.

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