MADRID, 21 (EUROPA PRESS)
A group of researchers at the University of Arizona (USA) has developed a new method for delivering chemotherapy drugs against pancreatic and breast cancer more effectively and with less damage to healthy tissue than standard forms of chemotherapy.
The article, published in Nature Cancer, shows that the new formulation of the drug paclitaxel developed by the research team could help overcome some common limitations of chemotherapy drugs, laying the groundwork for a new platform for the treatment of cancer and other diseases.
“Paclitaxel is potent and kills cancer cells, but to unleash its full therapeutic potential, we need to address its toxicity,” said Jianqin Lu, PhD, the John A. and Frances P. Ware Associate Professor in the R. Ken Coit College of Pharmacy at the University of Arizona.
"That means finding a better way to deliver the drug to tumor cells while also ensuring it remains there longer. This platform is based on a technology that modifies the drug so it better reaches and penetrates tumors, improving drug delivery and reducing side effects," the researcher added.
Paclitaxel, one of the mainstays of cancer chemotherapy, is used to treat a wide range of cancers, including breast, pancreatic, lung, and ovarian cancer. However, it has disadvantages, such as the fact that it often reaches unintended sites, such as the liver and spleen.
The new delivery method, which has been tested in mice, takes advantage of the unique properties of tiny fatty bubbles called nanovesicles, a type of nanoparticle that scientists commonly use in drug delivery. Lu's team chemically linked paclitaxel to sphingomyelin, a type of fat found in cell membranes, forming a nanovesicle.
According to the researchers, these structures allow the drug to be better delivered to the tumor and remain in circulation for longer, accumulating at the tumor site and less in healthy tissue.
The new formulation, called Paclitaxome, outperformed the chemotherapy drugs Taxol and Abraxane, also forms of paclitaxel, in tests against triple-negative breast cancer and advanced pancreatic cancer in mice. Researchers subsequently made further modifications and designed an improved formulation of paclitaxel (CD47p/AZE-Paclitaxome), which resulted in reduced tumor growth and improved survival.
"Many chemotherapy drugs have poor delivery. Paclitaxone is clinically promising because the system delivers the drug to the tumor site and prevents side effects. The drug isn't eliminated from the system as quickly. All of this improves its efficacy," said study co-author and oncologist Aaron Scott, MD, associate professor of medicine at the University of Arizona College of Medicine in Tucson.
THE ADMINISTRATION OF DRUG COMBINATIONS WAS ALSO IMPROVED
Thus, the modified paclitaxel also improved the delivery of drug combinations to tumors. The researchers tested the combination of paclitaxel and gemcitabine by inserting gemcitabine into the core of the nanovesicle. "We tested different drug ratios and then loaded the best one into the nanovesicle," Lu explains, adding that "the combination outperformed the co-administration of gemcitabine and Taxol, as well as the combination of Abraxane and gemcitabine."
In another trial, they combined modified paclitaxel and the drug carboplatin to prevent the recurrence of triple-negative breast cancer in mice, while eliminating disease that had spread to other parts of the body.
"This strategy can be applied to other drugs and other diseases as well. We applied this nanovesicle strategy to another chemotherapy drug, camptothecin, and it worked well in a mouse model of colon cancer. This demonstrated the generalizability of this technology to a range of drugs," Lu said.
The researcher believes the same approach could be used to deliver chemotherapy drugs alongside immunotherapies, which attempt to harness the immune system against cancer. His team is working to gather more preclinical data and better understand the platform's applications.
"Our goal is to advance this to first-in-human clinical trials. This platform can address a variety of tumor types for patients who desperately need better therapies," Scott concluded.
