| Magnetic targeted drugs (MTD) could provide the opportunity to limit side effects created from nonspecific systemic exposure, by reducing the total amount of drug administered as well as limiting circulation of the drug throughout the body, while still achieving an efficacious concentration at the desired site in the body. Therefore, MTD have got great and wide attention in the field of cancer treatment. However, at present the process preparing magnetic nanosized particles (MNP) for antitumor drug carrier demands simplification, and drug content, drug control release and magnetic targeting activity to tumor of MTD demands thorough investigation and substantial promotion.In this thesis magnetic Fe3O4 nano-particles (MNP) were synthesized from molysite, sodium hydrate and polyethylene glycol (PEG), by the method of co-precipitation and supercritical fluid drying technique (SCFD). The preparing technique and processes were simplified. The composition, structure and properties of MNP were investigated by the methods of FTIR, XRD, SEM, BET and VSM. A series of conditional experiments and a group of L3(4) orthogonal experiments were carried out. The ways and mechanisms of preparing conditions (the sequences of introduction of materials, molysite concentrations, the ratio of Fe2+/Fe3+, the ratio of overdosage of sodium hydrate, the quantity of introduction of PEG and reaction temperature) affecting evaluation indicaters of properties (the specific surface area, the suspending stabilization and magnetic respondence of aqueous suspensions of MNP) were studied. The results of the orthogonal experiments were analyzed with the gray relationship systemic method. The main conclusions were as follows:(1) MNP could be prepared with the simplified technique and processes, absorbed a little of PEG with abundant hydroxyl groups in the surface of MNP particles, and could be used as drug carrier.(2) the order of the extent of the preparing conditions affecting properties of MNP was the ratio of overdosage of sodium hydrate > the quantity of introduction of PEG> reaction temperature> the ratio of ferrous salt to ferric salt.(3) the specific surface area of MNP could reach 83.21m2/g, and the aqueous suspensions of MNP could be stable against precipitation in 5 minutes, and magnetic respondence could reach 9s/0.22T-cm, with the molysite concentrations in the range of 0.036-0.072 mol/L, the ratio of overdosage of sodium hydrate in the range of 0.0-0.5, the quantity of introduction of PEG in the range of 50-100 mg/ml, reactiontemperature in the range of 50-70 ℃.Magnetic targeted drugs (MTD) were synthesized from bovine serum albumin (BSA), MNP and fluorouracil (5-Fu), by the technique of emulsion-cladding. The methods of test and characterization of drug content and drug control release of MTD were designed. The composition, structure, diameters and morphology of MTD particles was investigated by the methods of FTIR, SEM and AAS. The relationships between targeting activity in vitro and MNP content, velocity of flow and magnetic field intensity were studied with the designed tester of targeting activity in vitro. The main findings were as follows:(1) the MTD particles were formed with a magnetic nucleus coated by a integrated BSA layer, so-called core/shell structure, and the coating was of integrity, a kind of chemical bonds were formed between the nucleus and the coatings.(2) The analysis of morphology showed that the MTD particles was spheric, the formation of so-called secondary particle in the course of BSA curing played an important roll of the broaden of the diameter distributions.(3) the drug content of MTD increased with the quantity of introduction of 5-Fu increasing, the extent of BSA curing and the effect of the drug control release was enhanced with the curing temperature elevated.(4) the targeting activity in vitro was enhanced with the MNP content of MTD increasing, played down with the velocity of flow getting bigger, and promoted with the magnetic field intensity i... |
PDF Full Text Request