By David Douglas
NEW YORK (Reuters Health) - In concert with the peptide iRGD, nanoparticles with hollow silica cores can enhance the delivery of irinotecan to a murine model of pancreatic ductal adenocarcinoma, according to California-based researchers.
This silacasome carrier for irinotecan "makes an improvement over the free drug by reducing the high level of drug toxicity, while enhancing treatment efficacy by delivering more drug to the pancreas cancer site in an animal model," Dr. Andre E. Nel told Reuters Health by email.
"The efficacy is enhanced," he added, "if the silicasome carrier is administered with separate injection of the iRGD peptide, because this leads to an additional three-fold increase in the amount of drug making it to the cancer site."
In an April 18 online paper in The Journal of Clinical Investigation, Dr. Nel of the University of California, Los Angeles, and colleagues note that although the disease is almost uniformly fatal, the introduction of nanocarriers that deliver irinotecan or paclitaxel has improved survival.
However, these have relied principally on abnormal leaky vasculature for tumor access. Another approach is to use a transcytosis transport pathway that is regulated by neuropilin-1 which can be triggered by iRGD.
The ability to increase drug delivery, Dr. Nel said, "depends on the effect of the peptide in opening up a transport system for taking the nanoparticles across the blood vessel wall at the cancer site."
In a mouse model of pancreatic ductal adenocarcinoma, coadministration of iRGD boosted the uptake of an irinotecan-loaded silicasome carrier and resulted in enhanced survival and markedly reduced metastasis.
Ultrastructural imaging showed that iRGD coadministration induced a vesicular transport pathway that carried silicasomes from the blood vessel lumen to a perinuclear site within the cancer cells. Silicasome uptake was also enhanced by iRGD in patient-derived xenografts.
Dr. Nel added, "We have also demonstrated in previous research that the silicasome drug platform can also be used for the delivery of other cancer drugs, including the combination of two drugs (gemcitabine and paclitaxel) that work together."
"We hope to take the treatment platform forward to human clinical trials," he concluded, "with the expectation that this could lead to prolonging survival for people with pancreas cancer."
J Clin Invest 2017.
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