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Development of dry gene powder for lung and evaluation of its efficacy

肺基因干粉的研制及其功效评价

基本信息

批准号：
15590050
负责人：
OKAMOTO Hirokazu
金额：
$ 1.79万
依托单位：
Meijo University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590050/
关键词：
gene therapy lung cancer drug delivery system inhalation interferon chitosan supercritical carbon dioxide dry powder

项目摘要

Recent y precipitation of powders with supercritical carbon dioxide- (SCF) has been attracting much attention as a method to produce tarry partides with high functionality We have already reported that the gene powders grew cl by the SCF prep bad improved stability and iir aced gene expression in lungs after intratracheal insufflation in mice. In the present study, we prepared chitosan-interferon β (DNA) powders by the SCF process to exannne the therapeutics of there in murinelung metastasis modelAn bus :solution of pCMV-MuBβ a plasmid DNA cabling murine intern β, and chitosan, a nonviral vector was dispersed in SCF with ethanol as a modifier to precipitate them. Mannitol was used as a powder vehicle. To establish a lung metasitatis, CT26, mouse colon carcinoma cells, were injected intravenously into mouse tail vein. The DNA powder or solution was administered intratracheally or intravenously to examine the lung weighty, number of metastatic nodules, and survival rate with time. The ge … More ne expression after intratracheal administration of DNA was abserved in normal and cancer tissue in the lung, while no expression was observed in the other organs. The DNA powders suppressed the increase in lung weight and number of nodules and prolonged the survival of the mice with smaller dose of DNA than DNA solutions. Intratracheal administration was more effective than intravenous administration. These findings suggested that the DNA powders prepared by the SCF processs had high therapeutic potential in murine lung metastasis model.The next study examined the stability of a gene in powers prepared with supercritical carbon dioxide (CO2) from the viewpoints of the ternary structure of DNA and in vivo inch potential. An aqueous chitosan-pCMV-Luc complex solution containing mannitol was injected into the stream of a supercritical CO2/ethanol admixture to precipitate a gene powder. The obtained gem powders and gene solutions were placed in stability chambers at 25 or 40゜C for 4 weeks. The integrity, and transfection potency of the gene were examined by electrophoresis and in van pulmonary transfection study in mice The supercritical CO2 process decreased the sided DNA doting the manufacturing process; however, the decrease in the remaining supercoiled and open circular DNA in the powders during storage was much slower than that in solutions. In addition, the powders had W war w on potency than the solutions containing the same amount of DNA. The effect of chitosan on the stability of DNA in solutions was not obvious in the solutions but it improved the stability of DNA in powders du manufacturing and storage. Thus, a gene powder with a vector is a promising formulation for a ready-to use inhalation therapy of pulmonary diseases. Less

近年来，超临界二氧化碳（SCF）沉淀法作为一种制备高功能性焦油状颗粒的方法受到了广泛关注。我们已经报道了用SCF制备的基因粉末在小鼠肺内吹气后生长良好，稳定性提高，并影响了肺内基因表达。本研究采用超临界流体技术制备壳聚糖-β-干扰素（chitosan-interferon β，DNA）复合物，以探讨其对小鼠肺转移瘤的治疗作用。甘露醇用作粉末载体。为了建立肺转移，将小鼠结肠癌细胞CT 26静脉内注射到小鼠尾静脉中。将DNA粉末或溶液经气管内或静脉内施用以检查肺重量、转移结节的数量和随时间的存活率。的ge ...更多信息经气管内注射DNA后，在肺正常组织和癌组织中观察到表达，而在其他器官中未观察到表达。与DNA溶液相比，DNA粉末抑制了肺重量和结节数量的增加，并延长了使用较小剂量DNA的小鼠的存活时间。肠内给药比静脉给药更有效。本研究从DNA的三元结构和体内微环境电位的角度，考察了超临界二氧化碳（CO2）法制备的DNA粉末中基因的稳定性。将含有甘露醇的壳聚糖-pCMV-Luc复合物水溶液注入超临界CO2/乙醇混合物流中以沉淀基因粉末。将获得的宝石粉末和基因溶液置于25或40 ℃的稳定室中4周。通过电泳和小鼠货车肺转染研究检查基因的完整性和转染效力。超临界CO2工艺减少了制造过程中的侧边DNA;然而，在储存期间粉末中剩余的超螺旋和开放环状DNA的减少比溶液中的减少慢得多。此外，粉末的效力比含有相同量DNA的溶液的效力更低。壳聚糖对DNA在溶液中的稳定性影响不明显，但能提高DNA在粉末中的稳定性。因此，具有载体的基因粉末是用于肺病的即用型吸入疗法的有前景的制剂。少

项目成果

期刊论文数量（14）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

ポストゲノム時代の微粒子吸入療法

后基因组时代的微粒吸入疗法

DOI：
发表时间：
2005
期刊：
粉体工学会誌 42(5)
影响因子：
0
作者：
Hirokazu Okamoto;岡本浩一;岡本浩一
通讯作者：
岡本浩一

Inhalation Therapy in the Post-Gnome Era

后侏儒时代的吸入疗法

DOI：
发表时间：
2005
期刊：
J.Soc.Powder Thchnol.Jap. 42(5)
影响因子：
0
作者：
Hirokazu Okamoto;岡本浩一;岡本浩一;Hirokazu Okamoto;Hirokazu Okamoto
通讯作者：
Hirokazu Okamoto

Development and Evaluation of Gene Powder for Inhalation Therapy of Lung Cancer

肺癌吸入治疗基因粉的研制与评价

DOI：
发表时间：
2005
期刊：
Bulletin of Research Institute of Meijo University 10(in press)
影响因子：
0
作者：
Hirokazu Okamoto;岡本浩一;岡本浩一;Hirokazu Okamoto
通讯作者：
Hirokazu Okamoto

Functional Microparticles of Medicies

药物功能微粒

DOI：
发表时间：
2004
期刊：
Nanotechnology with Supercritical Fluids (ed. by Tadafumi Adschiri) (CMC Press, Tokyo)
影响因子：
0
作者：
Hirokazu Okamoto;岡本浩一;岡本浩一;Hirokazu Okamoto;Hirokazu Okamoto;Hirokazu Okamoto
通讯作者：
Hirokazu Okamoto

肺がん治療を目的とした遺伝子ドライパウダーの開発と有効性の評価

治疗肺癌的基因干粉剂的研制及疗效评价