Pulmonary gene delivery by chitosan-pDNA complex powder prepared by a supercritical carbon dioxide process
Pulmonary gene delivery by chitosan-pDNA complex powder prepared by a supercritical carbon dioxide process
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DOI：
10.1002/jps.10285
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发表时间：
2003-02-01
影响因子：
3.8
通讯作者：
Danjo, K
中科院分区：
文献类型：
--
作者：
Okamoto, H;Nishida, S;Danjo, K
壳聚糖-质粒 DNA (pDNA) 复合粉末作为肺部基因。采用超临界二氧化碳（CO2）工艺制备了递送系统，并评估了其体内活性。以甘露醇为载体的粉末是通过将巨细胞病毒启动子驱动的荧光素酶表达质粒(pCMV-Luc)的水溶液分散在超临界CO2/乙醇混合物中，以壳聚糖作为阳离子载体或以壳聚糖作为阳离子载体来制备的。采用 V 形喷嘴的超临界 CO2 工艺成功生产了壳聚糖-pDNA 粉末。壳聚糖的添加抑制了超临界CO2过程中pCMV-Luc的降解并增加了粉末的产率。将粉末或 pCMV-Luc 溶液肺部给药后，评估小鼠肺中的荧光素酶活性。与不含壳聚糖的pCMV-Luc粉末或含或不含壳聚糖的pCMV-Luc溶液相比，壳聚糖-pDNA粉末增加了小鼠肺中的荧光素酶活性。 N/P 比 = 5 的壳聚糖-pDNA 粉末将荧光素酶活性提高至 pCMV-Luc 溶液的 2700%。这些结果表明含有壳聚糖的基因粉末是一种有用的肺部基因递送系统。 (C) 2003 Wiley-Liss, Inc. 和美国制药协会。
Chitosan-plasmid DNA (pDNA) complex powders as a pulmonary gene. delivery system were prepared with a supercritical carbon dioxide (CO2) process and their in vivo activity was evaluated. The powders with mannitol as a carrier were prepared by dispersing aqueous solutions of a luciferase expression plasmid driven by the cytomegalovirus promoter (pCMV-Luc) with or without chitosan as a cationic vector in a supercritical CO2/ethanol admixture. The supercritical CO2 process with a V-shaped nozzle successfully produced chitosan-pDNA powders. The addition of chitosan suppressed the degradation of pCMV-Luc during the supercritical CO2 process and increased the yield of powders. The luciferase activity in mouse lung was evaluated after pulmonary administration of the powders or pCMV-Luc solutions. The chitosan-pDNA powders increased the luciferase activity in mouse lung compared with pCMV-Luc powders without chitosan or pCMV-Luc solutions with or without chitosan. The chitosan-pDNA powder with an N/P ratio = 5 increased the luciferase activity to 2700% of that of the pCMV-Luc solution. These results suggest that gene powder with chitosan is a useful pulmonary gene delivery system. (C) 2003 Wiley-Liss, Inc. and the American Pharmaceutical Association.