Preparation And Biological Examination Of 5-Flurouracil Magnetic Chitosan Microspheres

Ferromagnetic micro-spheres consist of magnetic nanoparticles, which confers the drug carrier the property of magnetic responsiveness, and polymer carrier, which binds the intended anti-cancer drug. Such carriers are supposed to be targeted to the site of tumor by the applied magnetic field, and thus to achieve high local drug concentrations and reduce undesirable toxic side effects.The aim of the present investigation is to prepare 5-Fu magnetic chitosan microspheres (MCMs) by W/O (What is the full name? Whenever abbreviation appears, you should define the full name first, unless the abbreviation is commonly accepted.) emulsion/polymer cross-linking technique and optimize experimental condition and the achieved microspheres. In doing this, we have evaluated the microspheres properties, such as surface morphology, mean diameter, in vitro release and stability. Finally, the efficiency of MCM targeting in rabbits and the achieved pharmacokinetics in rats have also been assessed. These studies actually established the feasibility of using MCM as a practical carrier for targeted release of chemotherapeutical agents in cancer treatment. The results obtained are as follows: (1) The 5-Fu-MCMs were prepared under the optimized experimental parameters. It was well spherical in morphology with diameters of 4.9845±2.5127 (n=-500), 5-Fu loading efficiency of up to 60.5% and the time to achieve 50% drug release of 11.72h. The microspheres were stable at ≤25℃.(2) To study the distribution of MCMs at targeted organ vs. non-targeted organs, the Fe contents was determined in tissue slices with atom-absorption spectrum. The results indicate that the microspheres' diameter is appropriate for lung targeting, with high enough efficacy of passive targeting and no embolism and resort in capillaries. There was obviously preferential distribution at targeted site over no targeted sites. The MCM distribution with applied magnetic field was significantly different from that without applied magnetic field. These results demonstrated that the microspheres have well magnetic responsiveness for the passive targeting of the microspheres.(3) The microspheres were injected into the vein of rats to study the 5-Fu pharmacokinetics in vivo. It was found that 5-Fu in MCMs had a significantly higher T1/2 β(4.202h vs. 1.0022h) and AUC 25.2148 () h vs.17.3378 () h ) than that of direct 5-Fu injection. Experiments also indicated that MCMs targeted 5-Fu to lung with a notable efficacy, with a maximum percentage of 54.62% of the total 5-Fu loaded in MCMs distributed in lung 1 hour post injection.