Studies On Magnetic Solid Lipid Nanoparticle

Magnetite-loaded solid lipid nanoparticles (MSLN) represent a class of functional materials that may have potential for use in drug targeting. It is usually composed of a magnetic part and a solid lipid nanoparticles (SLN) part. The magnetic part is often an inorganic magnetite nanoparticles. The SLN part are particles made from solid lipids with a mean diameter between approximately 50 and 1000 nm. The magnetite-loaded solid lipid nanoparticles can be potentially used in drug targeting. Magnetite can be synthesized through co-precipitation of ferrous and ferric aqueous solution by addition of a base. Ibuprofen as insolubility model drug and CDDP as water-solubility model drug were studied for preparing Magnetite-loaded solid lipid nanoparticles (MSLN).The main research aspects are as follows:First Chapter:The preparation of oleic-acid-coated magnetite nanoparticles.Magnetite can be synthesized through co-precipitation of ferrous and ferric aqueous solution by addition of a base. In order to prevent them from possible oxidation in air as well as form agglomeration, the magnetite nanoparticles should be coated with oleic acid during precipitation process. At the same time that it can be increased its lipophilicity and consequently their incorporation into lipid phase. Effect of Fe3O4 magnetic nanoparticles products with different reaction temperature and concentration were investigated by single factor experiments. The optimal processes and formulation was obtained by orthogonal experiment design, based on the color, dispersibility and magnetic response time.The appearance was examined by FESEM and TEM, The results showed that oleic-acid-coated magnetite have well-defined spherical or elliptical shapes, which have a diameter of 7 nm. The XRD pattern of oleic-acid-coated magnetite is in good agreement with that of standard magnetite. The results of DSC-TGA indicate the Fe3O4 envelopment amount of oleic oil is about 7.05%, the oleic oil was chemical adsorbed on the surface of particle to form the primary layer. SQUID measurements indicated that the saturation magnetization at 5K and 300K is 71 emu/g and 63 emu/g. Second Chapter:Studies on Magnetic Solid Lipid Nanoparticles Loaded Ibuprofen (IB)The effects on the appearance and stability of IB-SLN of processes and formulations were investigated by single factor experiments. Two kind of optimal formulation were obtained by orthogonal experiment design, based on the encapsulate efficiency(EE%). Fe3O4 magnetic fluid were added optimal formulation of IB-SLN. Two kind of IB-MSLNs was finally acquired with the method of emulsification dispersion-ultrasound.The result of TEM showed that Two kind of IB-MSLNs were sphericity; the average size IB-MSLNⅠand IB-MSLNⅡwere (127±17) nm and (122±16)nm, respectively; and zeta potential were (-1.43±0.6) mV and (-16.1±5.53) mV, respectively; SQUID measurements indicated that IB-MSLN I and IB-MSLN II exhibited superparamagnetic behavior with a blocking temperature of 98 K and 78 K. The saturation magnetization at 5K and 300K for IB-MSLN I is 10.81 and 9.45emu/g and for IB-MSLNⅡis 3.57 and 2.86emu/g, respectively. the EE% of ibuprofen and ferroso-ferric oxide were 86.9% and 84.1%; the release of IB-MSLN was completely in the given mediums in 36h, which was according to Higuchi model.The formulations and processes of lyophilization were investigated basing on the appearance, color and redispersibility of IB-MSLNⅡ.IB-MSLNⅡsuspensions were administered into the cavity in a model of antigen-induced arthritic rabbit and evaluated with joint swelling and antibody titer to ovalbumin. IB-MSLN provided a conspicuous pharmacological efficacy in the joints of arthritic rabbits such as reducing joint swelling and antibody titer to ovalbumin. Ibuprofen-MSLN was better than ibuprofen-SLN in pharmacodynamics.Third Chapter:Studies on Magnetic Solid Lipid Nanoparticles Loaded CDDPThe effects on the appearance and stability of CDDP-SLN of processes and formulations were investigated by single factor experiments. The optimal formulation was obtained by orthogonal experiment design, based on the encapsulate efficiency(EE%). The Fe3O4 magnetic fluid, which was synthesized by co-precipitation method, was added in the formulation. The Magnetic Solid Lipid nanoparticles loaded CDDP (CDDP-MSLN) was finally acquired with the method of emulsification dispersion-ultrasound, with glycerin monostearate as lipid carrier, soybean phospholipids for injection, Pluronic F-68 and Tween80 as emulsifiers. CDDP-MSLN possessed a small size and an uniform particle size distribution, which were consistent with the demand of nano-preparations.The results of TEM showed that CDDP-MSLN was sphericity; the average size, zeta potential and EE% were (132±18) nm, (-13.3±6.94) mV and 75.9%, respectively; SQUID measurements indicated that CDDP-MSLN exhibited superparamagnetic behavior with a blocking temperature of 150 K. The saturation magnetization at 5K and 300K for CDDP-MSLN is 1.45 and 1.28 emu/g. The results of XRD was indicated that CDDP was embedded into MSLN with the form of amorphous; Results of release experiments showed that the release of CDDP-MSLN were completely in the given mediums, which was according to Weibull model. Besides, CDDP-MSLN was instable in 4℃and 25℃, therefore, the lyophilized products were necessary for storage.The formulations and processes of lyophilization were investigated base on the appearance, redissolution and redispersibility of CDDP-MSLN.A pre-column derivatization HPLC method was established for the in vivo assay of CDDP. Nickel chloride and diethyldithiocarbamate(DDTC) were employed as internal standard and derivatization agent, respectively. This method was proved to be specified and precise, which was fit for the in vivo assay of CDDP. Three different formulations, which included CDDP saline solution, CDDP-MSLN and CDDP-MSLN under applied magnetic field, respectively, were administrated i.v. in rats to examine their in vivo distributions. We can reach to a conclusion that CDDP-MSLN was able to gather to targeted areas and exhibited an obvious targeted effect under applied field, therefore the physical targeted effects were finally achieved.