Thermosensitive gemcitabine-magnetoliposomes for combined hyperthermia and chemotherapy

Nanotechnology. 2016 Feb 26;27(8):085105. doi: 10.1088/0957-4484/27/8/085105. Epub 2016 Jan 28.

Abstract

The combination of magnetic hyperthermia therapy with the controlled release of chemotherapeutic agents in tumors may be an efficient therapeutic with few side effects because the bioavailability, tolerance and amount of the drug can be optimized. Here, we prepared magnetoliposomes consisting of magnetite nanoparticle cores and the anticancer drug gemcitabine encapsulated by a phospholipid bilayer. The potential of these magnetoliposomes for controlled drug release and cancer treatment via hyperthermic behavior was investigated. The magnetic nanoparticle encapsulation efficiency was dependent on the initial amount of magnetite nanoparticles present at the encapsulation stage; the best formulation was 66%. We chose this formulation to characterize the physicochemical properties of the magnetoliposomes and to encapsulate gemcitabine. The mean particle size and distribution were determined by dynamic light scattering (DLS), and the zeta potential was measured. The magnetoliposome formulations all had acceptable characteristics for systemic administration, with a mean size of approximately 150 nm and a polydispersity index <0.2. The magnetoliposomes were stable in aqueous suspension for at least one week, as determined by DLS. Temperature increases due to the dissipation energy of magnetoliposome suspensions subjected to an applied alternating magnetic field (AMF) were measured at different magnetic field intensities, and the values were appropriated for cancer treatments. The drug release profile at 37 °C showed that 17% of the gemcitabine was released after 72 h. Drug release from magnetoliposomes exposed to an AMF for 5 min reached 70%.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / metabolism
  • Antimetabolites, Antineoplastic / pharmacology*
  • Cell Survival / drug effects
  • Delayed-Action Preparations / chemistry*
  • Delayed-Action Preparations / pharmacology
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / metabolism
  • Deoxycytidine / pharmacology
  • Drug Compounding
  • Drug Liberation
  • Drug Stability
  • Ferrosoferric Oxide / chemistry
  • Gemcitabine
  • Hyperthermia, Induced / methods
  • Light
  • Liposomes / chemistry*
  • Liposomes / pharmacology
  • Magnetic Fields
  • Magnetite Nanoparticles / chemistry*
  • Magnetite Nanoparticles / ultrastructure
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Particle Size
  • Photochemotherapy / methods
  • Primary Cell Culture
  • Rats
  • Rats, Inbred Lew

Substances

  • Antimetabolites, Antineoplastic
  • Delayed-Action Preparations
  • Liposomes
  • Magnetite Nanoparticles
  • Deoxycytidine
  • Ferrosoferric Oxide
  • Gemcitabine