Researchers have struggled with the challenge of getting oral medications past the treacherous environment of the gut intact and into the bloodstream where they can be most effective. But now Sylvester Comprehensive Cancer Center and University of Miami Miller School of Medicine researchers report success in accomplishing this breakthrough using nanotechnology.
In a new study published in the journal ACS Nano, Shanta Dhar, Ph.D., assistant director of technology and innovation at Sylvester and associate professor of biochemistry and molecular biology, Bapurao Surnar, Ph.D., a postdoctoral associate working with Dr. Dhar, and their colleagues report success using an innovative nanoparticle approach to deliver ivermectin orally to treat Zika infection.
“Getting through the barrier of the gut is pretty exciting for us,” Dr. Dhar said.
Admittedly, injecting a drug directly to the bloodstream would be simpler. In fact, Dr. Dhar noted, “most nanoparticles now are delivered intravenously.” But among the goals of the Miller School team were to offer greater convenience for patients, create a formulation with a stable shelf life, and verify the efficacy of an oral drug encapsulated in a nanoparticle until it reaches the bloodstream.
“When people get Zika or any kind of viral disease, we don’t want them to have to come to the clinic all the time,” Dr. Dhar said. Unlike injectable formulations, “we want to have an off-the-shelf treatment available – pills or capsules.”
The researchers also developed a powder formulation that remains stable and retains its therapeutic efficacy for up to six months, she added.
Regarding the efficacy of ivermectin delivered this way, “we have found that after 24 hours and up to 48 hours, it reaches therapeutic levels in the blood,” Dr. Surnar said. The study also showed that the nanoparticle delivery strategy results in a steady state, controlled release of ivermectin, thereby also avoiding the bolus effect possible with IV injections.
Efficacy is important, Dr. Surnar said. The ivermectin-loaded nanoparticles even showed anti-Zika virus effect in cell lines the researchers tested. “That’s a pretty amazing thing.”
Another advantage investigators found was that the nanoparticle-encapsulated ivermectin does not cross an in vitro placental barrier.
Following their proof-of-concept findings with ivermectin, their flexible nanoparticle strategy could offer safe passage to many other potentially life-saving oral drugs, Dr. Dhar said. “We can change the payload from ivermectin to your drug of choice.”
In fact, expanding the reach of this new strategy is the objective going forward. “We are definitely taking the platform forward and trying to use this for other viral diseases, such as HIV,” Dr. Dhar said. “We are also looking at its potential use in treating liver cancer.”
The team included Dushyantha Jayaweera, M.D., professor of medicine and senior associate dean for research; Sylvia Daunert, Pharm.D., M.S., Ph.D., chair of biochemistry and molecular biology and director of the Dr. John T. Macdonald Foundation Biomedical Nanotechnology Institute; and Sapna Deo, Ph.D., professor of biochemistry and molecular biology. Nagesh Kolishetti, Ph.D., assistant professor of immunology and nano-medicine at Florida International University, also participated in the research.
This study was financially supported by Sylvester Comprehensive Cancer Center and the Florida Department of Health.