Encapsulated IPA-3 in sterically stabilized liposomes (SSL). SSL-IPA-3 averaged 139 nm in diameter, polydispersity index (PDI) of 0.05, and a zeta potential of −28.1, neither of which changed over 14 days; however, the PDI increased to 0.139. Analysis of liposomal IPA-3 levels demonstrated good stability, with 70% of IPA-3 remaining after 7 days. SSL-IPA-3 inhibited prostate cancer cell growth in vitro with comparable efficacy to free IPA-3. Excitingly, only a 2 day/week dose of SSL-IPA-3 was needed to inhibit the growth of prostate xenografts in vivo, while a similar dose of free IPA-3 was ineffective. These data demonstrate the development and clinical utility of a novel liposomal formulation for the treatment of prostate cancer.
Researchers at the University of Georgia have created a new therapeutic for prostate cancer that has shown great efficacy in mouse models of the disease. The treatment is designed to inhibit protein PAK-1, which contributes to the development of highly invasive prostate cancer cells.
Aside from non-melanoma skin cancer, prostate cancer is the most common cancer among men in the U.S. It is also one of the leading causes of cancer death among men of all races. “PAK-1 is kind of like an on/off switch,” said A/Prof Somanath Shenoy. “When it turns on, it makes cancerous cells turn into metastatic cells that spread throughout the body.”
They developed a way to package and administer a small molecule called IPA-3, which limits the activity of PAK-1 proteins. IPA-3 was enveloped in a liposome and injected it intravenously. The liposome shell surrounding IPA-3 ensures that it is not metabolized by the body too quickly, allowing the inhibitor enough time to disrupt the PAK-1 protein.
This molecule significantly slowed the progression of cancer in mice, and it also forced the cancerous cells to undergo apoptosis. “When we first began these experiments, we injected IPA-3 directly into the bloodstream, but it was absorbed so quickly that we had to administer the treatment 7 days a week for it to be effective,” Shenoy said. “But the liposome that Dr. Cummings created makes the IPA-3 much more stable, and it reduced the treatment regimen to only twice a week.”
“The results of our experiments are promising, and we hope to move toward clinical trials soon,” he said, “but we must figure out what side effects this treatment may have before we can think about using it in humans.” http://news.uga.edu/releases/article/potential-treatment-for-prostate-cancer-0316/
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