Researchers with the Kansas City Veterans Affairs Medical Center and North Dakota State University have devised a new way to deliver pancreatic cancer drugs that can fight the disease much more easily. Taking cancer drugs in nanoparticles shows the ability to target tumors more effectively and avoid danger to other parts of the body.
The results of the study appeared in the journal Jan. 4, 2021, of the magazine Molecular Medications.
Veterans’ health care will benefit greatly from such therapeutic models, as they are effective in delivering the drug to the tumor site without any toxic side effects. [and with] dosing as less. When ready for use by patients, this procedure will reduce the number of doses a patient needs as well as effectively prevent tumor progression.. “
Dr. Sushanta Banerjee, Study Author and Researcher with Kansas City VA Medical Centers and the University of Kansas
Banerjee explains that this technology has the potential to significantly improve Veterans cancer care.
Pancreatic ductal adenocarcinoma is the most aggressive form of pancreatic cancer. It is one of the leading causes of cancer death worldwide. Patients with this type of cancer have a five-year survival rate of around 8%. Approximately 7% of cancer deaths in the United States result from pancreatic ductal adenocarcinoma.
The medicinal gemcitabine is the current level of care for the treatment of this cancer. However, gemcitabine offers little improvement in patients’ chances of survival. Gemcitabine rapidly degrades within the body, limiting its effectiveness. Pancreatic cancer tumors also often develop resistance to the drug.
More effective treatment for this type of cancer, called extracellular receptor kinase inhibitor (ERKi), has been developed. Genetic analysis has shown that specific gene mutation is one of the main drivers for pancreatic tumor growth. The ERK enzyme interacts with this movement, so the inhibition of the cancer enzyme can be reduced. Research also suggests an enhanced potency against gemcitabine in this enzyme.
Unfortunately, a number of complications make it difficult to treat patients with ERKi. The drug is toxic and can cause damage to other parts of the body. ERKi does not dissolve in water, making it difficult to prepare an effective form. It also tends to break down in the body, limiting its effectiveness.
To address these problems, the researchers devised a new method of delivering medications to pancreatic tumors. They designed a nanoparticle delivery system to get both gemcitabine and ERKi to the pancreas where they will be most effective.
Both drugs are encapsulated in nanoparticles made of polymers. The nanoparticles stop the drugs from breaking down and protect other areas of the body from the toxic effects.
The pH inside tumor cells is lower than the pH of the rest of the body. The nanoparticles are designed to release the drugs when they come in contact with a lower pH environment. In this way, the researchers can target the drugs specifically at cancer cells and not at other areas of the body.
Using a nanoparticle vehicle to deliver the medications will allow a higher dose to be delivered without the need for several individual doses, Banerjee said.
In the study, the researchers tested their new method on laboratory-bred cancer cells. Effectively deliver nanoparticle circulation of both drugs to the target cells. The experiment showed that this combination of drugs can suppress cancer cell growth. Results also showed that this method of delivery was “significantly” more efficient than dispensing the drugs without the nanoparticles.
In addition, the researchers found that adding ERKi to gemcitabine increased the body’s sensitivity to gemcitabine. Both drugs work together homogenously to fight cancer, according to the researchers.
While more research is needed, the study shows that the drug delivery method is a promising new method for fighting pancreatic cancer.
According to Banerjee, this method could also be used to treat other types of cancer, such as breast, prostate, and ovarian cancers. The nanoparticle polymers developed by the research team can be combined with various chemotherapy drugs to target tumors in different parts of the body, he explains.
The research team is currently working on different drug compounds to treat different cancers, and they are also creating new polymers to improve cancer treatment.
Source:
Veterans Affairs Research Communication
Magazine Reference:
Ray, P., et al. (2021) pH-Sensitive Carriers of Nanodrug for Codelivery of ERK Inhibitor and Gemcitabine promote tumor growth inhibition in pancreatic cancer. Molecular Medications. doi.org/10.1021/acs.molpharmaceut.0c00499.