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Study On Nanoparticles Contrast Agent For Liver Targeting In The MRI

Posted on:2004-10-15Degree:DoctorType:Dissertation
Country:ChinaCandidate:T F LiFull Text:PDF
GTID:1104360122990656Subject:Pharmacy
Abstract/Summary:PDF Full Text Request
A method of preparation of magnetite nanoparticles in ordered systems, as in vesicle and microemulsion, consisting of soybean lecithin and water has been introduced. The size of magnetite grain was controlled by the content of soybean lecithin and size of liposomes in the system. It was found by experiment that magnetite nanoparticles were formed inside the double layer vesicles. The magnetite nanoparticles were separated by magnetic separation and centrifugation and the dispersion of the magnetite nanoparticles prepared at 10 % (w/w) soybean lecithin was particularly stable. The formation of pure magnetite nanoparticles was confirmed by analyses of XRD and electron diffraction pattern.A method of preparation of magnetite nanoparticles in dextran solution has been introduced. The size of magnetite grain was controlled by the content of dextran in the system. The magnetite nanoparticles were separated by magnetic separation and centrifugation and the dispersion of the magnetite nanoparticles prepared at 10 % (w/w) dextran was particularly stable. The formation of pure magnetite nanoparticles was confirmed by analyses of XRD and electron diffraction pattern.NTCA are studied comprehensively and systematically. The research work can be divided into two parts in vivo and in vitro.This paper introduced a method of how to realize the Multiple Factor Optimization Technology that is based on Artificial Neural Networks and the application of this technology to the preparation of magnetite dextran contrast agent. The optimization effect was very good. It was expected to become an effective method to seek good conditions in pharmaceutical technology.NTCA is superparamagnetic and biodegradable, but the stability of NTCA isn t reported. The present work, we obtained an optimal formula by uniform design, then invested the stability of its injection. The results showed injection was stable when its pH is neutral, and it was insensitive to light radiation, the storage time was forecasted as 3 years according to classical thermotatical method.In the in vitro study work, we select material to prepare NTCA properly.This paper describes an inductively coupled plasma emission spectrometric method for the analysis of Fe in rat plasma to study the pharmacokinetics of NTCA in rats. Calibration curves were obtained in the range of 0.125-1.50 ug mL-1. The relative standard deviation ranges from 5.93% to 6.80%, and accuracy was between 87.6 and 102%. Dilution with water has no influence on the performance of the method, which could then be used to quantify Fe concentration in plasma up to 0.50 ug mL-1. The limit of quantification was 0.10 ug mL-1. At this level, the average relative standard deviation was 6.80%. The results indicated that the method meets the accuracy and precision requirements for the pharmacokinetic studies. The concentration of Fe in plasma was measured and the main pharmacokinetic parameters was calculated by Topfit 2.0 (GmbH. Shering AG, Godecke AG, Germany).These nanoparticles were evaluated for their ability to target to the liver in vivo. The tissue distribution of NTCA was evaluated following i.v administration in rats. Animals were sacrificed at different time and their tissues were collected and analyzed for iron content. The results of tissue distribution showed that liver targeting of the magnetite nonoparticle was demonstrated by large drug target index (TI) of 2-5 fold increase concentrated in liver and spleen compared to magnetite aqueous solution.In order to ensure the safety of preparation, we also study the physical-chemical characterization and the stability of it in the pharmaceutical test. NTCA is a brown liquid , its particle size being about 3-5nm, viscosity being 0.870mPa s at 25C and potential being O.OmV, which can meet the requirement of injection. From the test, we have got the conclusion that NTCA should be stored under the condition of room temperature.In vivo study includes tissue distribution, pharmacodynamics, and the safety of pharmaceutics.We also study the...
Keywords/Search Tags:magnetite dextran nanoparticles, soybean lecithin, Artificial Neural Networks, topfit, ICP, Liver targeting, MRI
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