Thermosensitive gemcitabine-magnetoliposomes for combined hyperthermia and chemotherapy

Full text: The combination of magnetic hyperthermia therapy with controlled release of chemotherapeutic agents in tumor may be a therapeutic procedure efficient with fewer side effects since drug bioavailability, tolerance and amount can be optimized. In this work, we prepared magnetoliposomes that consist of magnetite nanoparticles cores and the antitumoral drug gemcitabine enwrapped by a bilayer of phospholipid molecules. The possibility of use the corresponding formulation for controlled drug release and cancer treatment by taking advantage of its hyperthermic behavior was investigated. Magnetic nanoparticle encapsulation efficiency was dependent on the initial amount present at the encapsulation stage and to the best formulation we found 66%. We chose this formulation to study physical-chemical properties and to encapsulate gemcitabine. The mean size and distribution of the particle size were determined by dynamic light scattering and Zeta Potential was measured. All magnetoliposomes formulations, presented mean size values of about 150 nm and a polydispersivity index of < 0.2, thus having acceptable characteristics for systemic administration. Magnetic heating under an applied alternating magnetic field was investigated for different magnetic field intensity and the magnetoliposome investigated showed temperature variation appropriate to cancer treatments. In order to evaluate the thermosensitivity of magnetoliposomes as well as the release profile of gemcitabine, drug release was investigated at 37°C and under alternating magnetic field exposition for 5 min. The rate of drug released from magnetoliposomes under alternating magnetic field was 70%. However, at 37°C was only 17% after 72 hours. References: Gravem, H. Gemcitabine-containing liposomes. 2006. Dissertação (Mestrado em Fármacia) - Instituto de Fármacia, Universidade de Tromso, Tromso, 2006. Federico, C.; Morittu, V. M.; Britti, D.; Trapasso, E.; Cosco, D. Gemcitabine-loaded liposomes: rationale, potentialities and future perspectives. International Journal of Nanomedicine, v.7, p. 5423-5436, 2012. (author)