Bookmarkers beware: Bookmarks to pages other than the home page may not work after we change our server in April Editor's Choice | This Week in BMJ | Press releases BMJ No 7129 Volume 316 News Saturday 7 February 1998 More precise targeting of drugs in pipeline Three teams of researchers from Germany, France, and the United States have developed new and more precise ways of targeting drugs at diseased tissues. They report successfully using electric currents, tiny porous beads, and impregnated acetate discs to deliver large molecules - genes, antibodies, and proteins - directly to their targets, bypassing the gut and blood stream, where they would normally be broken down (Nature Biotechnology1998;16:159­71). These techniques, although not yet perfected in humans, have the potential to deliver small quantities of highly effective agents, including genes, into cancers and diseased coronary blood vessels without the side effects associated with pills and intravenous or intramuscular injections. Researchers are developing more precise drug delivery techniques Photo: PHILIPPE PLAILLY/SCIENCE PHOTO LIBRARY The German team, from the Max Planck Institute for Physiological Research in Bad Nauheim, used porous microspheres no bigger than the inside of a capillary to deliver fibroblast growth factor directly into the small vessel network in pig hearts. Fibroblast growth factor is a large protein which stimulates small blood vessels to regrow in diseased heart muscle. The researchers loaded the factor on to microspheres and injected them into a large coronary artery. Once the beads reached the capillary bed, they slowly released their cargo of growth factor without causing any damage to surrounding tissue and without obstructing blood flow. Because the drug is delivered to a precise area in very small doses, this technique of drug delivery avoids the serious side effects, such as low blood pressure, that occur when fibroblast growth factor is given by injection. Dr Wolf Ito, director of the institute, is hopeful that microsphere therapy can be adapted to treat patients with heart disease. "Enhancement of angiogenesis [growing new capillaries] would be particularly useful in patients who suffer from atherosclerotic disease in lots of small coronary vessels, although we have also shown that new capillary growth is sometimes useful when larger vessels are blocked." He warned, however, that microspheres do not dissolve, and no one yet knows whether they are safe enough over a lifetime to use in humans. In a second paper French scientists from the Institute of Structural Biology in Toulouse adapted an established laboratory technique to make cancer cells an easier target for gene therapy. They passed an electric current through melanomas in mice, making the melanoma cells leaky enough to admit genes and their proteins. The technique, known as electroporation, has been around for 40 years but scientists have only recently discovered its potential for getting drugs into cells. Clinical trials of electroporation in head and neck cancers in more than 50 patients have already shown that electric currents help the anticancer drug bleomycin to get inside and attack cancerous cells. These researchers used electroporation to admit much larger molecules; a marker gene and its protein, B galactosidase. They conclude that the technique is simple, safe, and a promising new approach to the biggest barrier in gene therapy - how to get destroyer genes into their target cells. According to Dr Justin Teissie, a scientist at the institute and an author of the paper, this is the first time the technique has worked for large molecules in live animals. It is safer, he said, than using viruses to carry genes into cells and more efficient than other experimental carriers being developed. An accompanying commentary points out, however, that only tumours on the body's surface are accessible to direct application of an electric current. For other deeper or disseminated tumours other delivery systems, such as carrier viruses, have greater potential. The final study in the trio looked at how mucosal surfaces like the vagina, which are weak spots in the body's defence against micro-organisms, can be fortified by local barrier of antibodies. The American researchers developed a small implantable acetate disc loaded with antibodies and studied the movement of antibodies through the vaginal wall in mice. They found that antibody levels around the wall and inside the vagina stayed high for several days. The study follows on from previous research showing that the same discs loaded with antibodies to the herpes virus can protect mice from herpes infection. Professor Elazer Edelman and Dr Mark Lovich from the Massachusetts Institute of Technology comment that the research offers a glimpse into the next generation of locally acting drugs. They speculate that it could pave the way for vaginal creams that protect against sexually transmitted viruses. Alison Tonks BMJ Home | Current issue | Past issues | Classified ads | Career Focus | Feedback Collections | About this site | About the BMJ | BMA | Medline