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Preparation and Biodistribution of Low-molecular-weight Chitosan Nanoparticles

Author: LiangJian
Tutor: HuFuQiang
School: Zhejiang University
Course: Pharmacy
Keywords: Chitosan Enzymatic hydrolysis Molecular weight Fluorescently labeled Nanoparticles Methotrexate Tissue distribution
CLC: R943
Type: Master's thesis
Year: 2003
Downloads: 542
Quote: 0
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Abstract


The carrier material of biocompatible and biodegradable drug delivery system resistance has an important meaning for non-parenteral administration, because these two characteristics is closely related to the safety of medication. In recent years, some research is dedicated to polymer materials through the gastrointestinal tract administered as a drug carrier. Chitosan (Chitosan, CS) having a biocompatible and biodegradable have been used in a pharmaceutical carrier. With the deepening of the study found that chitosan biodegradable in the body is not high, long-term use and easy to generate savings in the body, there are some problems in the blood compatibility and cell toxicity. The extent of these disadvantages and its N-acetylated chitosan, the molecular weight and other physicochemical properties of correlation. Therefore, the low molecular weight chitosan (low molecular weight chitosan, LMWC) as drug carriers start to be concerned. This topic choose low molecular weight chitosan as a carrier material of the gastrointestinal drug delivery systems. Obtained by enzymatic degradation and membrane separation technology different segment of molecular weight of the low molecular weight chitosan, the molecular weight of which is determined by the viscosity and gel permeation chromatography. PH sensitive test select at physiological pH environment that does not dissolve chitosan dissolved in the acidic environment within the tumor cells, the use of sodium tripolyphosphate (Tripolgphosphate SODIUM, TPP) as a coagulant to the ionic gelling method Preparation of chitosan nanoparticles (Chitosan nanoparticles, CS-NPs). The transmission electron microscope (TEM) and particle size and surface potential analyzer, examine the chitosan nanoparticles prescription and the impact of the process of its physical and chemical properties. Isothiocyanatobenzyl fluorescein (Fluorescein isothiocyanate, FITC) markers, chitosan isothiocyanato the fluorescein Thesis: Preparation and in vivo distribution of low molecular weight chitosan nanoparticles through chemical grafting different a chitosan polymer thiocyano fluorescein (FITC CS). Isothiocyanato-fluorescein prepared as a chitosan polymer nanoparticles carrier, after tail vein injection in mice by measuring the fluorescence intensity in the various tissues studied nanoparticles carrier in vivo distribution. To methotrexate Yin (Methotrexate, MTX) as a model drug, the preparation of drug-loaded chitosan nanoparticles investigated encapsulation efficiency by tail vein injection, Research chitosan nanoparticles tissue distribution of the drug in the body . Through control of the conditions of the enzymatic hydrolysis, five different molecular weight of the LMWC is separated by ultrafiltration, as determined by gel permeation chromatography, the weight average molecular weight (Mw) were 9 1000,72000,41500,21000 and 10300 in Dalton. PH sensitive test, select MW 21000 Dalton of low molecular weight chitosan as a carrier material, TPP ion gel method, was prepared by the shape class round ball, a narrow particle size distribution of nanoparticles. With the reduction of TPP concentration added to reduce the amount and the reduced amount of chitosan invested nanoparticles particle size decreases, but no significant change in Zeta potential values. To of preferred prescription and production process obtained MTx chitosan nanoparticles, the average particle size of 223.5 ± 121.onm zeta potential of 45.2 Guests 1.6mv 31.46 disabilities, the average drug encapsulation efficiency was 0.86% (n 3). Biodistribution results show FITC-a CS nanoparticles are injected via the tail vein of mice, nanoparticles have a certain degree of accumulation in the liver, kidney, spleen, and lungs, where the highest content in the liver nanoparticles; solution with MTX direct mouse tail vein injection compared, MTX after CS a NPS parcel, its half-life (tl / 2) in the blood by 1.O6h extended to 1.89h, in various tissues (liver, kidney, spleen, and lung) content increased significantly longer duration of action.

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