PREPARATION AND CHARACTERIZATION OF DEXTRAN MAGNETITE-INCORPORATED THERMOSENSITIVE LIPOSOMES - AN ONLINE FLOW SYSTEM FOR QUANTIFYING MAGNETIC RESPONSIVENESS

Purpose. Dextran magnetite (DM)-incorporated thermosensitive liposomes , namely thermosensitive magnetoliposomes (TMs), were prepared and cha racterized in order to investigate their possibility for magnetic drug targeting. Methods. TMs containing calcein were prepared at various D M concentrations by reverse-phase evaporation of dipalmitoylphosphatid ylcholine (DPPC). They were evaluated for their physicochemical proper ties including size, DM capture, magnetite distribution within liposom es, and temperature-dependent calcein release. Moreover a novel on-lin e flow apparatus with a sample injector, a coil of tubing placed in an electromagnet, and a fluorescence detector was developed for quantify ing the magnetic responsiveness of TMs. This device allowed us a real- time measurement of percentage holding of TMs by magnetic field. Resul ts. Due to water-soluble property of DM, higher contents of magnetite up to 490 mg per mmol DPPC were successfully incorporated into the lip osomes with DM than with conventional magnetite (Fe3O4). Thermosensiti vity and lipid integrity of TMs were not influenced by inclusion of DM . Using the on-line flow system, percentage holding of TMs by magnetic field was shown to vary with several factors; it increases as the mag netic field strength increases, the fluid flow rate decreases, the mag netite content increases, and the liposome concentration increases. Ty pically, at 490 mg incorporated magnetite per mmol DPPC, 0.5 ml/min-fl uid flow rate, and high magnetic field strength (greater than or equal to 10 kiloGauss), approximately 100% of TMs were found to be held. Co nclusions. The TMs were suggested to be useful in future cancer treatm ent by magnetic targeting combined with drug release in response to hy perthermia.