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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
  • 51 Downloads

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.

Keywords

Chitosan Targeted drug delivery Iron oxide nanoparticles Nanocomposite Echocardiography Heart failure 

Abbreviations

OM

Omecamtive Mecarbil

HF

Heart failure

MI

Myocardial infarction

PECAM-1

Platelet endothelial cell adhesion molecule

cTnI

Cardiac troponin I

Ang II

Angiotensin II

SPION

Superparamagnetic iron oxide nanoparticle

FDA

Food and drug administration

Nd

Neodymium

Fe

Iron

B

Boron

ICP

Inductively coupled plasma

HR-TEM

High resolution transmission electron microscopy

VSM

Vibrating sample magnetometer

DI

Deionized

HPLC

High performance liquid chromatography

TEM

Transmission electron microscopy

Fe-SEM

Field emission scanning electron microscopy

MTT

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

OD

Optical density

PBS

Phosphate buffer saline

LVID

Left ventricular internal dimension

LVPW

Posterior wall thickness

IVS

Interventricular septal thickness

ESV

End systolic volume

SV

Stroke volume

HR

Heart rate

FS

Fractional shortening

EF

Ejection fraction

CO

Cardiac output

DMEM

Dulbecco’s modified eagle’s medium

FBS

Fetal bovine serum

DMSO

Dimethyl sulfoxide

NBF

Neutral buffered formalin

H&E

Hematoxylin and eosin

MT

Masson’s trichrome

EE

Encapsulation efficiency

Notes

Acknowledgments

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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