Chemically modified drug shows promise for HIV treatment and elimination
IN a significant breakthrough that could hasten an eventual HIV cure, a research team at the University of Nebraska Medical Centre has changed the chemical structure of an existing antiviral drug to facilitate it in reaching cells and tissues where HIV resides.
The discovery is detailed in the February 5 issue of Nature Communications, one of Nature Research's leading biomedical research journals.
Using a physiochemical scheme that alters the properties of the drug dolutegravir, UNMC scientists took the modified drug and placed it into nanocrystals. The produced drug crystals easily distributed throughout the body to tissue reservoirs of HIV infection.
The advanced drug scheme extended the life of the drug and its entry into "hidden body compartments," from the muscle site of injection while increasing its action in reducing viral growth. The tissues included the lymph nodes, the bone marrow, the intestine and the spleen.
The modified drug crystals were not toxic, did not break apart with temperature changes and were stable for months of time. All organs and bodily functions remained intact after treatment.
Coated with parts of fat, the crystals efficiently maneuvered through cell protective membranes and were stored inside cells for weeks said Howard Gendelman, M.D., professor and chair, who with Benson Edagwa, Ph.D., assistant professor, co-led the study in UNMC's Department of Pharmacology and Experimental Neuroscience (PEN).
Once stored inside cells called macrophages, the drug was slowly released from the crystal in an altered inactive form called a "prodrug." The cell then breaks the prodrug into an active drug, and the active drug is then released into the circulation from the cell and tissue stores.
"The strength of this system is that it not only can be effective in improving HIV care and prevention," said, Dr. Edagwa, who designed the drug chemical modifications, "but can be applied to many classes of drugs beyond HIV, such as drugs used to treat cancer, other infectious diseases and degenerative diseases that affect the brain."-SCIENCEDAILY