Scientists have developed a way to deliver cisplatin nanoparticles to treat nonmuscle-invasive bladder cancer. In newly published animal studies, they show the approach is less toxic than treatment with regular cisplatin and, potentially, more efficacious.
In short, the use of intravesical cisplatin nanoparticles reduces cancer cell proliferation while limiting drug absorption beyond the bladder barrier, according to early findings published online in Clinical Cancer Research (Aug. 14, 2017).
“One of the reasons that intravesical chemotherapy is thought not to work very well in certain patients is more of a drug delivery problem than an actual chemotherapy problem. Most chemotherapy—when you give it intravesically—does not actually get into the bladder,” said Max Kates, MD, of the James Buchanan Brady Urological Institute and Johns Hopkins University School of Medicine, Baltimore. “So, we designed a platinum-based drug that has increased absorption into the bladder. By modifying chemotherapy to improve bladder absorption, we might make these drugs more effective in our bladder cancer patients.”
Dr. Kates and colleagues tested the delivery model, comparing it to regular cisplatin treatment and no treatment, by conducting a series of in vitro and in vivo studies in murine models.
To start, they delivered cisplatin nanoparticles through a catheter, directly into the animals’ bladders, or used the traditional cisplatin catheter delivery approach. Four hours post administration, they found the bladders of animals that received nanoparticles had more than 20 times better drug absorption than the animals receiving the regular drug. Nanoparticle administration also resulted in at least two to three times less systemic absorption than with the regular drug.
The authors then administered the drug-infused nanoparticles or regular cisplatin to mice’s bladders by catheter once per week for 3 weeks. Detectable levels of the drug’s platinum were identified in the blood of mice in the regular cisplatin group, but not among the mice receiving nanoparticles—confirming the finding that the nanoparticle formulation is associated with less systemic absorption.