Polyhydroxybutyrate-Coated Magnetic Nanoparticles for Doxorubicin Delivery: Cytotoxic Effect Against Doxorubicin-Resistant Breast Cancer Cell Line


Yalcin S., Unsoy G., MUTLU P. , Khodadust R., GÜNDÜZ U.

AMERICAN JOURNAL OF THERAPEUTICS, vol.21, no.6, pp.453-461, 2014 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 21 Issue: 6
  • Publication Date: 2014
  • Doi Number: 10.1097/mjt.0000000000000066
  • Title of Journal : AMERICAN JOURNAL OF THERAPEUTICS
  • Page Numbers: pp.453-461
  • Keywords: PHB, doxorubicin, magnetic nanoparticles, targeted drug delivery, drug resistance, DRUG-DELIVERY, MICROSPHERES, RELEASE, POLYHYDROXYALKANOATES, CARDIOTOXICITY, DEGRADATION, SYSTEMS, WATER, DNA

Abstract

In this study, polyhydroxybutyrate (PHB)-coated magnetic nanoparticles (MNPs) were prepared by coprecipitation of iron salts (Fe2+ and Fe3+) by ammonium hydroxide. Characterizations of PHB-coated MNPs were performed by Fourier transform infrared spectroscopy, x-ray diffraction, dynamic light scattering, thermal gravimetric analysis, vibrating sample magnetometry, and transmission electron microscopy analyses. Doxorubicin was loaded onto PHB-MNPs, and the release efficiencies at different pHs were studied under in vitro conditions. The most efficient drug loading concentration was found about 87% at room temperature in phosphate-buffered saline (pH 7.2). The drug-loaded MNPs were stable up to 2 months in neutral pH for mimicking physiological conditions. The drug release studies were performed with acetate buffer (pH 4.5) that mimics endosomal pH. Doxorubicin (60%) released from PHB-MNPs within 65 hours. Doxorubicin-loaded PHB-MNPs were about 2.5-fold more cytotoxic as compared with free drug on resistant Michigan Cancer Foundation-7 (human breast adenocarcinoma, MCF-7) cell line (1 mu M doxorubicin) in vitro. Therefore, doxorubicin-loaded PHB-MNPs lead to overcome the drug resistance.