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The Study of Aerosol Gene Delivery System

Author: PanZuoNa
Tutor: XuYuHong
School: Shanghai Jiaotong University
Course: Pharmacy
Keywords: CDAN / DNA complexes Reverse micelle Quantitative aerosol Distributed Transfection efficiency
CLC: R94
Type: Master's thesis
Year: 2008
Downloads: 46
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Abstract

Viral respiratory infectious diseases has become a serious global public health and safety issues. Gene therapy may become a new effective antiviral treatment strategies. Must be found to achieve good gene therapy, in particular to gene therapy for respiratory diseases, effective delivery of the carrier and a delivery method. The present study is more non-viral vectors, such as liposomes and micelles, are water-soluble, not in the aerosol propellant miscible, which greatly limits the application of the aerosol in the respiratory disease. Solve the above problems, it is required to prepare formulations that can be miscible with the propellant, and the respiratory tract are widely distributed while increase gene expression. We developed a new type of lipid gene complex. We first oil-water two-phase extraction system plasmid DNA through electrostatic interaction with the lipid complex (CDAN reverse micelles), extracted from the organic phase, and then characterized the preparation. The combination of UV spectrophotometric determination of the extraction rate by gel electrophoresis, particle size was measured with a laser particle size analyzer and atomic force microscopy the morphology of the reverse micelles. Experimental results show that the preparation of plasmid DNA carrying rate is 80% or more, the light intensity distribution of the average particle diameter of 150nm, was dissolved in anhydrous diethyl ether can be dispersed into the Freon propellants give a clear solution. The formulations may be formed with the propellant aerosol ejected after filling Withstand quantitative aerosol. Furthermore, the method based on two provisions of the 2005 version of \and so on. The results show that the aerosol can reach the quantitative requirements, the droplet particle size is between 1 ~ 5μm. Thereafter, we have carried out of reverse micelles aerosol in cell and animal models of gene transfection experiments, proved to ensure the survival of the cells at the same time, having a high transfection efficiency. The distribution of the experimental results of the in vitro model of the human respiratory tract show a wide distribution of the aerosol. Biodistribution experiments, fluorescence imaging results show that the reverse micelle aerosol can be widely distributed in the respiratory tract and lungs of the mice. Cells and in vivo transfection experiments confirmed the formulation can effectively enhance the expression level of the reporter gene in airway epithelial cells. This thesis solve the problems of the present, most gene vectors can not be miscible with the propellant, and a new type of lipid-DNA complexes were prepared, and can ensure the complete and effective gene while, to improve transfection efficiency. Further, the use of quantitative aerosol is more convenient, and can achieve an effective distribution of the contents in the respiratory tract. Accordingly, the present study provides for the prevention and treatment of viral respiratory promising novel lipid delivery vectors and methods.

The Study of Aerosol Gene Delivery System

Abstract

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