May 30, 2006
Stabilizing Liposomes with Nanoparticles
Drug-loaded liposomes were the first engineered nanoparticles to find clinical utility in treating cancer patients, but the initial promise they showed has not translated well into a wide range of anticancer agents. One of the major limitations they suffer from is that they tend to fuse with one another in watery environments, such as blood, leaking their payload while forming far larger particles and agglomerations that cannot reach tumor cells and that the body excretes rapidly. As a result, other types of nanoparticles that do not suffer this fate have largely replaced liposomes as a favorite among drug developers.
In a somewhat ironic twist, Steven Granick, Ph.D., and graduate student Liangfang Zhang from the University of Illinois, Urbana, have used positively charged polymer nanoparticles to stabilize liposomes and prevent them from fusing with one another. The results of this work appear in the journal Nano Letters.
Preparing hybrid liposome-nanoparticle proved to be simple. The investigators first prepared standard liposomes and then mixed them with smaller carboxylated polystyrene nanoparticles in a ratio of 1 liposome per 100 nanoparticles and sonicated this mixture for 10 minutes. They then concentrated the resulting dilute suspension of the desired hybrid by blowing nitrogen gas over the preparation. Nanoparticles cover approximately 25 percent of the liposome surface, leaving a large area of the liposome available for attaching drugs and targeting molecules.
Tests conducted one day after preparing the hybrids showed that virtually no fusion or clumping had occurred even in highly concentrated suspensions. In fact, tests as long as 50 days after preparation showed that the hybrids remained stable. Additional tests with liposomes loaded with a fluorescent dye found that no leakage occurred over four days. Longer duration studies are now underway.
This work is detailed in a paper titled, "How to stabilize phospholipid liposomes (using nanoparticles)." An abstract of this paper is available through PubMed.