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Keywords:

  • plasmid DNA;
  • chitosan;
  • supercritical carbon dioxide;
  • dry powder;
  • gene delivery system

Abstract

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. © 2003 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 92:371–380, 2003