|Howard Gendelman, M.D.|
"Using UNMC's advanced cell biology and imaging technologies combined with cutting edge nanotechnologies, we have engineered an anti-HIV drug nanoformulation with available HIV-combating drugs and fed macrophages large amounts of it," said Howard Gendelman, M.D., the senior scientist for this research team and chair of UNMC's Department of Pharmacology and Experimental Neuroscience.
"Then, as macrophages migrate to tissues where HIV grows, drug is secreted by the macrophage. In this way the same cell that spreads virus infection could also stop viral growth and reduce the toxicities commonly seen by conventional pills."
The nanoparticle drug formulation packaged into one of the body's immune macrophages was tested on humanized mice that have their immune systems replaced with human cells. Results showed that a single dose could reduce the virus and protect the immune system.
The research appears simultaneously this month in four different highly regarded or emerging biomedical research journals - Blood, Virology, The Journal of Leukocyte Biology and The Journal of Neuroimmune Pharmacology.
"The potential of this line of research is extraordinary," said Huanyu Dou, M.D., who is program director in neurovirology at UNMC's Deparment of Pharmacology and Experimental Neuroscience and played a key role in the studies. "To give a single injection once a month could permit new treatment opportunities for those who poorly tolerate conventional drug regimens or have already failed standard therapies. If proven to be effective in humans, the implication of potential lower costs through fewer drug dosages and associated distribution costs is also promising, particularly for developing countries."
"This research offers hope for increased patient compliance by reducing the burden of frequent dosing, side effects and limited efficiency in reaching the virus in difficult areas of the body, such as the brain," Dr. Gendelman said.
Despite the significant impact of anti-retroviral therapy (ART), the worldwide HIV-1 pandemic continues to grow. An estimated 40 million people are infected around the world, the majority in developing countries. Although ART has reduced disease morbidity and increased life expectancy, global access to ART is limited by drug expenses, treatment failures and dosing complexities.
Multiple daily dosing regimens that are not followed by patients and numerous side effects block long-term HIV-1 suppression in infected people. Additionally, continuous viral suppression requires maintenance of therapeutically effective drug concentrations. Total elimination of the virus in an infected person has not yet been achieved.
The nanoformulations used in this study were developed at Baxter Healthcare Corporation, and the research was a result of the work of more than 10 scientists over the past three years. Clinical studies are planned within the next several years once approvals and further toxicity studies are completed.
"This approach also could be effective in other applications such as destroying cancer cells, but unlike traditional chemotherapy, it could allow normal cells to remain functional and disseminate the drug," said Sasha Kabanov, Ph.D., professor and director of the Center for Drug Delivery and Nanomedicine (CDDN) at UNMC. "If proven to be effective in humans, this research could be a significant development for HIV/AIDS therapy, and I look forward to our future collaboration."
The key to the success of this work rested in an interdisciplinary research team of investigators that included immunologists, physical chemists, pharmacologists, physicists, biologists and virologists. R. Lee Mosley, Ph.D., Michael Boska, Ph.D., and Santhi Gorantla, Ph.D., were principal members of the UNMC scientific team, which led the imaging studies. Collaborations in support of measurements of anti-retroviral drugs were done with Christopher Destache, Pharm.D., professor of pharmacy practice at Creighton University's School of Pharmacy.
The work was supported by Baxter Healthcare Corporation and by research grants from the National Institute of Neurological Diseases and Stroke and the National Institute of Mental Health.