Drug delivery to the heart with tannin acid may avoid surgery

Treating cardiovascular and related vascular diseases using tannin acid injections may avoid the need for surgery, reveals a new study from the Korea Advanced Institute of Science and Technology (KAIST).

Researchers developed a heart-targeting drug delivery technology using tannin acid via intravenous systemic injection. The method can be applied to the development of a variety of new protein-based drugs, according to the research team.

Joint research leader Professor Haeshin Lee, from the Department of Chemistry, said, "Although there have been numerous drugs related to heart disease, so far, there has not been efficient drug delivery to the heart. So, this technology will be able to reformulate existing drugs into new and more efficient drugs."

Cardiovascular-circulatory disease is the second leading cause of death in Korea. The disease typically leads to myocardial infarctions caused by poor oxygen and nutrient supply due to narrowed coronary arteries and poor blood flow to the heart.

Chemotherapeutic drugs

Conventional methods of drug delivery to the heart need surgical procedures involving incisions in the chest wall and bones. Clinics still rely on surgical procedures despite many research projects which have focused on developing chemotherapeutic drugs and therapeutic proteins. Drug delivery can be an alternative but is challenging because the ceaseless pulsing of the heart and big exchanges of blood mean administered therapeutics do not stay inside the heart very long, said the researchers.

The researchers selected tannic acid – known for giving bitter taste to wines and one of the most abundant polyphenols found in plants – because of  properties enabling its use as a multifunctional coating molecule. Prof Lee and his team developed protein and peptide therapeutics with tannic acid and succeeded in targeting protein and peptide therapeutics to the heart.

Coated on the surface of a granulated protein complex, tannic acid helped to maintain cardiac function because it adhered to extracellular matrices, elastin, and collagens in heart tissues. This enabled the protein to stay attached to the heart tissue for longer.

Cardiac toxicity

Tannic-acid-modified proteins stayed in blood vessels five days longer compared with protein-only injections, according to the team. They also found that tannic acid protein complexes do not show cardiac toxicity and do not cause noticeable pathology.

The team is continuing to develop biomaterials for medical applications by testing various polyphenolic materials that feature adhesive and coating properties, including tannic acid. A mixture of tannic acid and fibroblast growth factors were injected into animal models with myocardial infarctions.

After four weeks, they confirmed that the infarction was reduced and the left ventricular pressure and cardiac output achieved almost normal levels.

The joint research leader was Dr Ki-Suk Kim from the institute’s Predictive Model Research Center.

The research was published in Nature Biomedical Engineering.

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