The first trial to test a targeted nanoparticle capable of controlling a drug’s release is now under way in humans. The tiny particles were designed to deliver the chemotherapy drug docetaxel, used to treat lung, prostate, and breast cancers, among others.
Using nanoparticles allows researchers to deliver a higher dose of cancer drugs directly to tumors but reduces toxicity to patients. In mouse models, the amount of docetaxel delivered to tumors was seven times higher in mice infused with docetaxel nanoparticles compared with traditional docetaxel. In addition, the researchers saw a greater reduction in tumor mass in mice that received docetaxel nanoparticles. Side effects were no worse with the nanoparticles than with the traditional, unpackaged chemotherapy drug.
In other animal studies, researchers found that docetaxel nanoparticles circulated in the bloodstream much longer and the drug remained safely encapsulated inside the nanoparticle shell while in the bloodstream. Also, docetaxel nanoparticles did not accumulate in the liver, an unwanted occurrence that is almost always seen with other nanoparticles.
Based on those previous studies, researchers started a phase I clinical trial in people with solid tumors that have not responded to a range of chemotherapies to determine the maximum tolerated dose of a targeted nanoparticle called BIND-014. Although the trial is ongoing, early data from the first 17 patients show that the nanoparticle exhibits antitumor activity and is generally well tolerated.
Researchers found that in the 48 hours after treatment, docetaxel concentration in the patients’ blood was 100 times higher with the nanoparticles as compared to docetaxel administered in its conventional form. The higher blood concentration resulted in tumor shrinkage in patients, in some cases with doses of BIND-014 that corresponded to as low as 20% of the amount of traditional docetaxel normally given. The nanoparticles were also effective in cancers in which docetaxel usually has little activity, such as cervical cancer and cancer of the bile ducts.
Researchers found that in the 48 hours after treatment, docetaxel concentration in the patients’ blood was 100 times higher with the nanoparticles as compared to docetaxel administered in its conventional form. The higher blood concentration resulted in tumor shrinkage in patients, in some cases with doses of BIND-014 that corresponded to as low as 20% of the amount of traditional docetaxel normally given. The nanoparticles were also effective in cancers in which docetaxel usually has little activity, such as cervical cancer and cancer of the bile ducts.
The study’s researchers had to develop a new nanoparticle design. Previously, researchers had tried to modify a prototype nanoparticle’s characteristics by attaching molecules for tumor cell binding. The problem with this process is the lack of reproducibility for small changes in design related to batch-to-batch variability, meaning that they could not create nanoparticles that differed from each other very narrowly to find the right pharmaceutical parameters.
To address that problem, researchers created a library of more than 100 unique nanoparticles. The nanoparticles start out as a long string of molecules, each with different functions—for example, holding and releasing the chemotherapy drug, hiding the nanoparticle from the immune system, or binding to tumor cells. Small changes can be made to any of the molecules in the string before assembly, creating small variations that can be screened for the desired properties of a drug-delivery vehicle. After those properties are added to the string, the chemotherapy drug is added to create a precisely designed nanoparticle in a highly reproducible way.
In the future, it is hoped that nanomedicines like this will lead to more manageable and effective chemotherapies. In addition, it may be possible to revisit drugs that failed in clinical trials in the past because they were too toxic, if nanoparticles make it possible to deliver them in a safer way.
Contributor Deborah McBride, RN, MSN, CPON®, is a staff nurse IV at the Kaiser Permanente Oakland Medical Center and an assistant professor at Samuel Merritt University in Oakland, CA. Read more articles by Deborah McBride Fonte: ONS Connect
