A simple change in electric charge may make the difference between someone getting the medicine they need and a trip to the emergency room—at least if a new study bears out. Researchers investigating the toxicity of particles designed to ferry drugs inside the body have found that carriers with a positive charge on their surface appear to cause damage if they reach the brain.
These particles, called micelles, are one type of a class of materials known as nanoparticles. By varying properties such as charge, composition, and attached surface molecules, researchers can design nanoparticles to deliver medicine to specific body regions and cell types—and even to carry medicine into cells. This ability allows drugs to directly target locations they would otherwise be unable to, such as the heart of tumors. Researchers are also looking at nanoparticles as a way to transport drugs across the blood-brain barrier, a wall of tightly connected cells that keeps most medication out of the brain. Just how safe nanoparticles in the brain are, however, remains unclear.
So Kristina Bram Knudsen, a toxicologist at the National Research Centre for the Working Environment in Copenhagen, and colleagues tested two types of micelles, which were made from different polymers that gave the micelles either a positive or negative surface charge. They injected both versions, empty of drugs, into the brains of rats, and 1 week later they checked for damage. Three out of the five rats injected with the positively charged micelles developed brain lesions. The rats injected with the negatively charged micelles or a saline control solution did not suffer any observable harm from the injections, the team will report in an upcoming issue of Nanotoxicology.
Knudsen speculates that one of the attributes that makes positive micelles and similar nanoparticles such powerful drug delivery systems may also be what is causing the brain damage. Because cells have a negative charge on their outside, they attract positively charged micelles and bring them into the cell. The micelles’ presence in the cell or alteration of the cell’s surface charge, she says, may disrupt the cell’s normal functioning.
Negatively charged nanoparticles can also enter cells, according to other research. However, they do so less readily and must be able to overcome the repulsion between themselves and the cell surface. It is possible that the reason the negatively charged micelles were not found to be toxic was that they did not invade cells to the same extent as the positively charged micelles.
The findings are intriguing, says biomedical engineer Jordan Green of Johns Hopkins University in Baltimore, Maryland. But he cautions that there is no evidence that all positively charged nanoparticles behave this way. Other factors can also play a role in the toxicity of nanoparticles, adds pharmaceutical expert Jian-Qing Gao of Zhejiang University in Hangzhou, China. The size and concentration of the particles, as well as the strain of rat used, could all have influenced the results, he says.