A combined low-frequency electromagnetic and fluidic stimulation for a controlled drug release from superparamagnetic calcium phosphate nanoparticles: potential application for cardiovascular diseases

J R Soc Interface. 2018 Jul;15(144):20180236. doi: 10.1098/rsif.2018.0236.

Abstract

Alternative drug delivery approaches to treat cardiovascular diseases are currently under intense investigation. In this domain, the possibility to target the heart and tailor the amount of drug dose by using a combination of magnetic nanoparticles (NPs) and electromagnetic devices is a fascinating approach. Here, an electromagnetic device based on Helmholtz coils was generated for the application of low-frequency magnetic stimulations to manage drug release from biocompatible superparamagnetic Fe-hydroxyapatite NPs (FeHAs). Integrated with a fluidic circuit mimicking the flow of the cardiovascular environment, the device was efficient to trigger the release of a model drug (ibuprofen) from FeHAs as a function of the applied frequencies. Furthermore, the biological effects on the cardiac system of the identified electromagnetic exposure were assessed in vitro and in vivo by acute stimulation of isolated adult cardiomyocytes and in an animal model. The cardio-compatibility of FeHAs was also assessed in vitro and in an animal model. No alterations of cardiac electrophysiological properties were observed in both cases, providing the evidence that the combination of low-frequency magnetic stimulations and FeHAs might represent a promising strategy for controlled drug delivery to the failing heart.

Keywords: ELM stimulation; QRS complex; bioreactor; cardiac cells; drug delivery; drug release.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiovascular Diseases* / drug therapy
  • Cardiovascular Diseases* / metabolism
  • Cardiovascular Diseases* / pathology
  • Cell Line
  • Delayed-Action Preparations / chemistry
  • Delayed-Action Preparations / pharmacokinetics
  • Delayed-Action Preparations / pharmacology
  • Drug Carriers* / chemistry
  • Drug Carriers* / pharmacokinetics
  • Drug Carriers* / pharmacology
  • Durapatite* / chemistry
  • Durapatite* / pharmacokinetics
  • Durapatite* / pharmacology
  • Electromagnetic Fields*
  • Humans
  • Magnetite Nanoparticles* / chemistry
  • Magnetite Nanoparticles* / therapeutic use
  • Male
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / pathology
  • Rats, Sprague-Dawley

Substances

  • Delayed-Action Preparations
  • Drug Carriers
  • Magnetite Nanoparticles
  • Durapatite