Targeted and Controlled Drug Delivery to a Rat Model of Heart Failure Through a Magnetic Nanocomposite.

Abstract

As a novel cardiac myosin activator, Omecamtive Mecarbil (OM) has shown promising results in the management of systolic heart failure in clinical examinations. However, the need for repeated administration along with dose-dependent side effects made its use elusive as a standard treatment for heart failure (HF). We hypothesized that improved cardiac function in systolic HF models would be achieved in lower doses by targeted delivery of OM to the heart. To test this hypothesis, a nanocomposite system was developed by composing chitosan and a magnetic core (Fe₃O₄), loaded with OM, and directed toward the rats' heart via a 0.3 T magnet. HF-induced rats were injected with saline, OM, and OM-loaded nanocomposite (n = 8 in each group) and compared with a group of healthy animals (saline injected, n = 8). Knowing the ejection fraction (EF) of healthy (93.68 ± 1.37%) and HF (71.7 ± 1.41%) rats, injection of nanocomposites was associated with improved EF (EF = 89.6 ± 1.40%). Due to increased heart targeting of nanocomposite (2.5 folds), improved cardiac function was seen with only 4% of the OM dose required for infusion, while injecting the same dose of OM without targeting was unable to stop HF progression (EF = 55.33 ± 3.16%) during 7 days. In conclusion, heart nanocomposites targeting improves the EF by up to 18% by only using 4% of the doses traditionally used in treating the HF.