Drug Combination Delivered by Nanoparticles May Help Prevent Resistance in Melanoma

Microscopic particles accumulate inside tumors

The first in a new class of medication that delivers a combination of drugs via nanoparticles may help prevent melanoma from becoming resistant to treatment, according to researchers at the Penn State College of Medicine. CelePlum-777 combines the nonsteroidal anti-inflammatory drug celecoxib (Celebrex, Pfizer, and generics) and the toxin plumbagin.

Celecoxib and plumbagin work together to kill melanoma cells when administered in a specific ratio, according to the researchers. The team used microscopic nanoparticles to deliver the drugs directly to cancer cells. The particles are several hundred times smaller than the width of a hair and can be loaded with medications.

“Loading multiple drugs into nanoparticles is one innovative approach to deliver multiple cancer drugs to a particular site where they need to act, and have them released at that optimal cancer cell-killing ratio,” said lead author Dr. Raghavendra Gowda. “Another advantage is that by combining the drugs, lower concentrations of each that are more effective and less toxic can be used.”

Celecoxib and plumbagin cannot be administered orally because the drugs have low bioavailability when taken in that manner, the investigators noted. Moreover, when given orally, the drugs cannot be used together in the necessary ratio because of potential toxicity to the patient. CelePlum-777, however, can be injected intravenously without toxicity.

Because of their small size, the nanoparticles accumulate inside tumors, where they release the drug combination to kill cancerous cells.

The researchers reported their findings in the journals Molecular Cancer Therapeutics and Cancer Letters.

“This drug is the first of a new class, loaded with multiple agents to more-effectively kill melanoma cells, that has potential to reduce the possibility of resistance development,” said senior author Dr. Gavin Robertson. “There is no drug like it in the clinic today, and it is likely that the next breakthrough in melanoma treatment will come from a drug like this one.”

The researchers reported the effects of CelePlum-777 on cancer cells in vitro and in murine tumors after intravenous injection. The drug prevented tumor development in mice with no detectable adverse effects and prevented proteins from promoting the uncontrolled growth of cancer cells.

More research is required by the FDA before CelePlum-777 can be tested in clinical trials. The Penn State researchers have patented their discovery and have licensed the drug-loaded nanoparticles to Cipher Pharmaceuticals, which will perform the next series of FDA-required tests.

Source: Penn State College of Medicine; March 15, 2017.