"Smart" Carriers And Tiny Skin-Deep "Medicine Cabinets" Improve Drug Effectiveness Against Cancer, AIDS, Other Diseases

The two systems based on polymer (plastic) technology are being detailed by the scientists this week (Oct. 21-25) in a series of more than 30 research papers at the 2001 American Association of Pharmaceutical Scientists' (AAPS) annual meeting in Denver. AAPS is a professional scientific society of more than 11,000 members employed in academia, industry, government and other research institutes worldwide.

The "smart" polymer, taken orally as a pill or injected, can be targeted to release its drugs in specific organs or cells by means of "ligands," a variety of compounds that interact only with the receptors on certain types of cells, said Patrick J. Sinko, chairman of the department of pharmaceutics in Rutgers' College of Pharmacy.

"We attach the drug or drugs to the polymer and then we attach the ligand," said Sinko. "The ligand is like the address on a package, making sure the polymer with its drug or package of drugs goes directly to the diseased cell." When it reaches its destination, the ligand hooks up to the cell surface and permits the polymer and its drug cargo to pass into the cell, the researcher said.

Sinko and his collaborators, Michael Leibowitz and Stanley Stein of UMDNJ-Robert Wood Johnson Medical School, have also shown that without the targeting ligands, the drug-polymers are unable to penetrate cells, a discovery that led to the first patent for a drug-delivery system this past summer plus many pending patents.

When injected under the skin, the polymer gel drug carrier forms a tiny lump or "button" that serves as a minuscule medicine cabinet, delivering multiple drugs to patients in a controlled fashion over days, weeks or years, Sinko said. "The gel is ideal for certain types of patients, such as elderly patients or schizophrenic patients who tend to forget to take their medicines, or for certain kinds of injected drugs where a controlled release significantly improves therapeutic outcomes," Sinko said.

When the button is gone, the patient or care giver knows that it is time to get another injection, Sinko said, "an important consideration for patients who may not be able to manage their medications on their own." Animal tests have proven so promising that a company, Theraport Biosciences, based in East Brunswick, has been formed to further develop the technology in cooperation with, and under license to, the universities. The firm ultimately plans to market the targeted drug-delivery system under the name TheraBus and the gel system under the name TheraGel.

Using polymers to transport drugs has overcome another basic problem of pharmacology: Most drugs are fatty compounds that don't dissolve in water and are therefore difficult for body tissues to absorb. Putting them inside a polymer matrix makes them water soluble and gives them better pharmaceutical properties, the researchers found.

For example, Sinko noted, until now, camptothecin, a powerful drug designed to fight cancer, has not been marketable because it is virtually insoluble and difficult for the body to absorb. "But attaching it to a smart polymer drug carrier not only made it soluble and useable, it made the drug 30 to 50 times more potent."

The smart polymer has also proven highly effective in delivering a powerful AIDS-fighting peptide known as TAT inhibitor, which previously could not reach diseased body cells because peptides are destroyed by the body's digestive processes. In addition, even when they reach AIDS-infected cells, peptides can't easily penetrate them.

Because the polymer protects the TAT inhibitor within the body until it has reached its targeted cells, it has made the drug a potentially powerful weapon against AIDS, Sinko said. "In laboratory testing, it was as effective or more effective than many AIDS drugs on the market today."