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

  • Nasim Kiaie
  • Shahriar Hojjati EmamiEmail author
  • Shahram Rabbani
  • Rouhollah Mehdinavaz Aghdam
  • Hossein Ahmadi TaftiEmail author
Original Article


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.


Chitosan Targeted drug delivery Iron oxide nanoparticles Nanocomposite Echocardiography Heart failure 



Omecamtive Mecarbil


Heart failure


Myocardial infarction


Platelet endothelial cell adhesion molecule


Cardiac troponin I

Ang II

Angiotensin II


Superparamagnetic iron oxide nanoparticle


Food and drug administration








Inductively coupled plasma


High resolution transmission electron microscopy


Vibrating sample magnetometer




High performance liquid chromatography


Transmission electron microscopy


Field emission scanning electron microscopy


3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromidefor


Optical density


Phosphate buffer saline


Left ventricular internal dimension


Posterior wall thickness


Interventricular septal thickness


End systolic volume


Stroke volume


Heart rate


Fractional shortening


Ejection fraction


Cardiac output


Dulbecco’s modified eagle’s medium


Fetal bovine serum


Dimethyl sulfoxide


Neutral buffered formalin


Hematoxylin and eosin


Masson’s trichrome


Encapsulation efficiency



The authors would like to thank Dr. Alireza Imani at Physiology Department, Faculty of Medicine, Tehran University of Medical Sciences, for saving our time and expenses by suggesting ISO for HF induction.

Conflict of interest

None declared.

Supplementary material

10439_2019_2394_MOESM1_ESM.pdf (183 kb)
Supplementary material 1 (PDF 182 kb)


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Copyright information

© Biomedical Engineering Society 2019

Authors and Affiliations

  • Nasim Kiaie
    • 1
  • Shahriar Hojjati Emami
    • 1
    Email author
  • Shahram Rabbani
    • 2
  • Rouhollah Mehdinavaz Aghdam
    • 3
  • Hossein Ahmadi Tafti
    • 2
    Email author
  1. 1.Department of Tissue EngineeringAmirkabir University of TechnologyTehranIran
  2. 2.Research Center for Advanced Technologies in Cardiovascular Medicine, Tehran Heart CenterTehran University of Medical SciencesTehranIran
  3. 3.Schools of Metallurgy & Materials Engineering, College of EngineeringUniversity of TehranTehranIran

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