The development of a probe to measure the body’s immune function could lead to more accurate, individualized doses for cancer patients prescribed nanoparticle-based drugs, according to research conducted at the University of North Carolina.
Nanoparticles – drugs encapsulated in carriers measured at the scale of a one billionth of a meter – were developed as a method to deliver more chemotherapy to to specific tumor sites within the body. One major downside of this class of drugs is that the ability of a patient to remove the drug from the body can vary widely from patient to patient and thus lead to variability in response.
In a paper published online by the Journal of Pharmacology and Experimental Therapeutics , William Zamboni, PharmD, PhD, associate professor in the UNC Eshelman School of Pharmacy and member of the UNC Lineberger Comprehensive Cancer Center, in collaboration with Paola Gehrig, MD, and colleagues in UNC Gynecologic Oncology Program, outlines how a UNC-developed probe that measures the function of the mononuclear phagocyte system (MPS) can help determine the proper dosage of nanoparticle-based drugs to administer to patients.
Using a blood sample, researchers were able to use a chemical probe and method developed at UNC to track a direct relationship between MPS function and clearance of the nanodrug pegylated liposomal doxorubicin (Doxil®) in both animal models and in patients with ovarian cancer.
“You could use this probe to individualize the dose of nanoparticle agent that a patient should be administered,” said Zamboni.
While most conventional drugs are cleared from the body by the liver and kidneys, nanoparticles are engulfed and cleared by the monocytes, macrophages and dendritic cells that make up the MPS. Because the function of the MPS is highly variable across patients, the ability of physicians to predict the proper dosage for nanodrugs is more difficult than with conventional pharmaceuticals.
“The more active the MPS system, the faster these drugs are cleared from a patient,” said Zamboni.
By establishing the linkage between MPS function and the clearance of Doxil, Zamboni’s lab hopes to build a data set that will allow researchers and clinicians to develop better methods to establish dosing guidelines for Doxil and other the nanodrugs. Doxil, the first Food and Drug Administration (FDA) approved nanodrug, has been in clinical use since 1995. Because of the difficulty of measuring body-specific doses, patients using Doxil can experience strong side effects such as the sloughing off of skin from the palms and feet. The high interpatient variability in the clearance and effects (toxicity and efficacy) appears to occur with most nanoparticle anticancer agents.