• Design and development of heparin-based Nano micelles for delivering amiodarone in the treatment of cardiac arrhythmias
  • Hossein Naderi-Manesh,1,* Asma Hamidi,2 Maryam Nikkhah,3 Zahra Vaezi,4 Mohsen Sharifi,5
    1. Department of Biophisic, Faculty of Biological Science, Tarbiat Modares University, Tehran, Iran, Postal codes: 14115-154, Tehran, Iran
    2. Department of Nanobiotechnology, Tarbiat Modares University
    3. Department of Nanobiotechnology, Faculty of Biological Science, Tarbiat Modares University, Tehran, Iran, Postal codes: 14115-154, Tehran, Iran
    4. Department of Bioactive compounds, Faculty of Interdisciplinary Science and Technologies, Tarbiat Modares University, Postal codes: 14115-154, Tehran, Iran
    5. Department of Plant Biology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran


  • Introduction: Amiodarone is a class III antiarrhythmic agent that inhibits the abnormal heart rhythm by suppressing potassium currents. Its notable adverse effects include thyroid dysfunction, pulmonary toxicity, and hepatotoxicity. Formulating amiodarone in the inner core of a Nano-emulsion through a self-Nano-emulsifying drug delivery system (SNEDDS) can reduce these side effects while enhancing the therapeutic efficiency of the drug. Water-soluble polysaccharide heparin can be modified with fatty acid to form monodisperse self-assembled Nano-micelles in aqueous media.
  • Methods: Within this study, the hydrophobic derivatives of heparin were prepared by conjugating palmitic acid (Hep-Pal) via covalent amide binding and were characterized using Fourier-transform infrared spectroscopy (FTIR) and Nuclear Magnetic Resonance (NMR). The Hep-Pal nano-emulsion was prepared through the self-emulsification method in phosphate-buffered saline (PBS) at pH 7.4 and was characterized further by dynamic light-scattering (DLS), zeta potential measurement, and field emission scanning electron microscopy (FE-SEM). The amiodarone was subsequently entrapped in the hydrophobic core of the Hep-Pal micelle through the process of lipid-Nano-emulsion formulation, and the encapsulation efficiency and release profile were evaluated.
  • Results: The presence of a peak at 1750 cm⁻¹ in the FTIR spectra confirmed an amide bond in the heparin-palmitic acid conjugation, . which further confirmedby, the characteristic peak at 7.8 ppm in HNMR spectra. The formulated nano-emulsions exhibited particle size in the range of 20-35 nm with a spherical morphologyand the zeta potential −38 mV, indicating good colloidal stability. Drug content of the amiodarone-loaded nano micelles was 90.25 ± 0.58 % at 37 ◦C, which demonstrated a more sustained release profile compared to the initial phase: 25% release at 10 h, 55% at 30 h, and 95.12% at 70 h.
  • Conclusion: We have developed a novel nanomicelles carrier for amiodarone delivery to treat abnormal heart rhythm, In vitro analysis of drug release from the nanomicelles indicated that the system is able to control amiodarone release in the medium and it localized specifically to hydrophobic spaces. Furthermore, the synergistic effect of bioactive compounds will investigate.
  • Keywords: heparin-based carrier, Self-Nano-emulsifying drug delivery system (SNEDDS), amiodarone,