A research team lead by Professor Haeshin Lee of the KAIST Department of Chemistry discovered an effective method of targeting drugs at the heart via injection with tannic acid. The study, a joint effort with Professor Kisuk Kim’s team from the Predictive Model Research Center at Korea Institute of Toxicology, was published in the May issue of Nature Biomedical Engineering.

Cardiovascular diseases — diseases relating to the heart and its nearby systems — are the second leading cause of death in South Korea. Significant research was dedicated towards protein and peptide therapeutics for these diseases, but effective delivery remained to be a challenge. While injection is the typically favored method of drug delivery for most cases, it is not viable for delivery into the heart because of the heart’s constant contraction and relaxation motion and changes in volume. Previously, this difficulty necessitated invasive surgical procedures in order to locally target the heart. Professor Lee’s method eliminates this inconvenience by providing an intravenous injection method that is effective for targeting the heart.

Tannic acid is an established polyphenol that naturally occurs in fruits, vegetables, and nuts; it is especially known for creating the astringent flavor in wines. The research team utilized the strong attraction between tannic acid and proteins to suggest a strategy of combining the therapeutic proteins with tannic acid. Tannic acid can also bind to elastin and collagen, which make up most of the myocardium. The strategy — dubbed TANNylation — succeeded in delivering proteins into the heart when injected in mice, whereas non-TANNylated injections failed to target the heart and ended up in the liver. In the specific case of myocardial infarction drugs, TANNylated injections decreased the size of infarction and improved cardiac output and pressure of the left ventricle after four weeks.

“Although various drugs were developed for cardiovascular disease, developments towards efficient delivery of these drugs have been relatively limited,” Professor Haeshin Lee remarked. “This is original technology that can be used to reformulate preexisting drugs into newly modified drugs.” TANNylation will likely become a crucial technology in augmenting treatments for cardiovascular diseases.