New Drug Delivery Methods in Spotlight

Early-phase treatment modalities -- ranging from a stem cell attack on metastatic cancer to what may be a true silver bullet against pulmonary infection -- were highlighted at the annual meeting of the American Thoracic Society.

The studies are all in the preclinical stages but could represent "exciting" new approaches to a range of illnesses, according to Beth Laube, Ph.D., of Johns Hopkins University School of Medicine, who moderated a press conference at which the studies were discussed.

The stem cell study combines two separate areas of research, according to Michael Loebinger, M.D., of University College London.

On one hand, he said, it has been known for some time that mesenchymal stem cells in bone marrow have the ability to home in on and bind to tumor cells.

On the other, he said, researchers have known that the molecule dubbed TNF-related apoptosis-inducing ligand -- or TRAIL -- kills cancer cells but not normal cells.

Combining the two using genetic engineering, Dr. Loebinger told reporters, the new cells induced programmed cell death in vitro in a variety of cancer cells, including lung, squamous cell, breast, and cervical cancer cells, while leaving normal cells intact.

In mice, Dr, Loebinger said, injections of the cells reduced tumor growth significantly (at P<0.001 p="0.03)">

"The two different aspects of this therapy have been used in humans," he said, but not together. TRAIL, for instance, has been used in phase I and II trials and appears to be safe.

The combination," he said, "is quite promising" and would be applicable to a wide range of cancers. Dr. Laube said the experiments are "very, very exciting," not least because of the ability of the cells to seek out and destroy tumor cells wherever they are in the body. "That's got to be helpful to patients," she said. Another new treatment modality targeted cystic fibrosis. In CF, the ion channel defects reduce airway surface liquid, which results in reduced mucociliary clearance and recurrent infections, said Andrew Hirsh, Ph.D., of Parion Sciences in Durham, N.C. One treatment that is sometimes used is the sodium channel blocker amiloride (Midamor), but it has several disadvantages, Dr. Hirsh said, including a relatively short effective span that requires frequent use.

Dr. Hirsh was reporting preclinical data on a new sodium channel blocker, dubbed GS-9411, that he said was 100 times more potent than amiloride (in terms of the 50% inhibition concentration). The drug also was able to maintain 85% of sodium channel blockage after multiple washes, compared with less than 10% for amiloride, which should translate to longer effective time in the body, he said.

The drug, delivered as an aerosol, is now in phase I clinical trials with healthy volunteers, Dr. Hirsh said. Meanwhile, researchers led by Carolyn Cannon, M.D., Ph.D., of Washington University School of Medicine in St. Louis, are studying how to deliver tiny nanoparticles containing silver compounds to lung infections. So-called silver carbene complexes have been shown to have antibiotic activity and one developed by Dr. Cannon and colleagues -- SCC1 -- is now the subject of an investigational new drug application, she said.

For technical reasons, that compound can't be put in nanoparticles, which she and colleagues thought would allow them to reduce the dose and number of doses needed to achieve a clinical effect. So they synthesized another molecule -- dubbed SCC22 -- which could be loaded into nanoparticles of L-tyrosine polyphosphate and delivered using a nebulizer.

In mice infected with Pseudomonas aeruginosa, Dr. Cannon said, 100% survived if they were treated intranasally with the SCC-loaded particles, while all of the untreated mice died.

The survival advantage left the researchers "surprised and thrilled," Dr. Cannon said. With the nano approach, she said, the mice could be given a smaller dose of the compound and be treated only once a day, compared with twice a day for the drug alone. Although the drug was tested in vivo against P. aeruginosa, Dr. Cannon said, it has been shown in vitro to be "effective against every bacterial species tested to date." It has not escaped her notice, she said, that -- if the animal studies are replicated in humans -- the compounds will be a true silver bullet against bacteria.

Source : www.medpagetoday.com