The Study On Preparation And Pharmacodynamic Of 5-Fluorouracil Magnetic Solid Lipid Nanoparticles

Magnetic targeted drugs can effectively reduce the toxic effect of chemotherapy drugs to improve efficacy, which have demonstrated a very bright prospect in the treatment of malignant tumors. In this paper, the research and development of magnetic targeted drugs delivery system was reviewed; the preparation of Fe3O4 magnetic nanoparticles and 5-fluorouracil magnetic solid lipid nanoparticles was introduced and the inhibitory effect of 5-fluorouracil magnetic solid lipid nanoparticles on H22 liver cancer solid tumor was studied.5-fluorouracil was expected to concentrate in tumor target tissue, release positioning and reduce side effect.1,The preparation of Fe3O4 magnetic nanoparticlesChemical co-precipitation method was adopted to prepare Fe3O4 magnetic nanoparticles with FeCl3·6H2O, FeSO4·7H2O, ammonia as the raw materials. Single factor tests were designed to study the influence of preparation conditions (pH, reaction temperature, concentration of iron salt, Fe3+/Fe2+, aging time) on the size, magnetic response and colour of Fe3O4 magnetic nanoparticles. On this basis, an orthogonal test was used to optimize the preparation. The results indicated that the more ideal technical process was as follows:the mechanical stirring rate was 1000r/min for 30 min at 65℃maintaining pH value in the range of 9～10, the concentration of Fe3+ was 0.2mol/L, Fe3+/Fe2+ was 1.25:1, with SDS as surfactant. After 30min mechanical stirring and ultrasonic dispersion, the aging time was 3h at 65℃. Under these conditions, the magnetic Fe3O4 nanoparticle was black, particle size was 15.72nm and response time in the strength of the magnetic field for the 1000Gauss was 48.67s. The composition of the products was tested by chemical analysis to find that the proportion of Fe3+/Fe2+ was 1.96:1, which was slightly less than 2. The structure and particle size of Fe3O4 was characterized by means of XRD and SEM. The results showed that the Fe3O4 magnetic nanoparticles were spherical, whose XRD pattern was consistent with Fe3O4 standard diffraction pattern.2,The preparation of 5-fluorouracil magnetic solid lipid nanoparticles To improve the therapeutic efficacy and reduce the toxicity of 5-fluorouracil (5-FU),5-fluorouracil magnetic solid lipid nanoparticles (5-FU-MSLN) were prepared by a W/O/W double emulsion solvent evaporation technique, using monostearin as the carrier, hydrogenated soybean lecithin and poloxamer as emulsifier, magnetic Fe3O4 nanoparticles as magnets. Single factor tests were designed to study the influence of preparation on the size, Zeta potential, encapsulation efficiency of 5-FU-MSLN to set the initial preparation. Base on the single factor tests, with the index of encapsulation efficiency, the preparation process was optimized by orthogonal test. The best preparation condition was:the monostearin content was 4.0%, the ratio of drug to lipid ratio was 1/10, the hydrogenated soybean lecithin to monostearin was 1/10, the Fe3O4 magnetic nanoparticles dosage was 0.1%, emulsifying temperature was 55℃, emulsifying time was 1h, the ultrasound power of foremilk was 400W last 30s, the ultrasound power of final milk was 200W last 60s. The result showed that the average diameter in size, PDI, Zeta potential, drug encapsulation efficiency of 5-FU-MSLN were 81.49nm,0.151,-25.28mV,58.35%. TEM presented 5-FU-MSLN as spherical particles, evenly distributed; 5-FU-MSLN were observed under the inverted microscope, whose vitro magnetic responsiveness was good. Such magnetic solid lipid nanoparticles seem appropriate for vascular administration followed by drug targeting.3,The inhibitory effect of 5-FU-MSLN on H22 liver cancer tumor-bearing miceThe aim was to evaluate the inhibitory effect of 5-FU-MSLN on the growth of H22 liver cancer solid tumor in mice. Fifty Kunming mice with H22 liver cancer solid tumor were divided into 5 groups evenly at random, namely, saline control group,blank magnetic solid lipid nanoparticles group,5-FU solution group,5-FU-MSLN group(without magnetic field) and 5-FU-MSLN group(plus magnetic field), which were received tail vein injection for seven days. The living condition of mice was observed everyday and the body weight and tumor volume were measured every other day. After the administration, the mice were killed in each group through cervical dislocation and the tour was stripped, weighed to calculate inhibition rate. The pathology of tumor was examined through conventional biopsy and the VEGF, Ki-67, MVD of tour were detected by SP immunohistochemical staining. 5-FU-MSLN group (plus magnetic field) was compared with other groups:the tumors grew slowly, tumor weight compared with the significant difference, VEGF, Ki-67, MVD detection and each group has a significantly compared to differences. The results show that 5-FU-MSLN (plus magnetic field) can significantly inhibit tumor growth.5-FU-MSLN was prepared with Fe3O4 magnetic nanoparticles which had good biocompatibility for the magnets, whose process was stable, meeting the needs for drugs. The drug in tumor-bearing mice under the influence of external magnetic field can locate and release, whose efficacy was improved. The results showed that 5-FU-MSLN was prospective for a new formulation.