[Local and systemic delivery of high-molecular weight drugs by powder inhalation].
The pulmonary route has recently attracted attention as a noninvasive administration route for peptide and protein drugs, and an insulin powder for inhalation was approved by authorities in Europe and the USA. The present study examined usefulness of insulin and gene powders for systemic and local inhalation therapy. We prepared several dry insulin powders by spray drying to examine the effect of additives on insulin absorption. Citric acid appears to be a safe and potent absorption enhancer for insulin in dry powder. However, in the powder with citric acid (MIC0.2 SD) insulin was unstable compared with the other powders examined. To improve insulin stability, a combination of insulin powder and citric acid powder was prepared (MIC Mix). MIC Mix showed hypoglycemic activity comparable to MIC0.2 SD while the insulin stability was much better than that of MIC SD. Next, dry insulin powders with mannitol were prepared with supercritical carbon dioxide (SCF); the powder thus prepared reduced blood glucose level rapidly and was more effective than that prepared by spray drying. Chitosan-pDNA complex powders as a pulmonary gene delivery system were also prepared with SCF and their in vivo activity was evaluated. The addition of chitosan suppressed the degradation of pCMV-Luc during preparation and increased the storage stability. The luciferase activity in mouse lung was evaluated after pulmonary administration of the powders. The chitosan-pDNA powder with an N/P ratio=5 increased the luciferase activity to 27 times that of the pCMV-Luc solution. These results suggest that gene powder with chitosan is a useful pulmonary gene delivery system.
Okamoto
Hirokazu
H
Faculty of Pharmacy, Meijo University, Nagoya, Japan. okamotoh@ccmfs.meijo-u.ac.jp
Danjo
Kazumi
K
D000042:Absorption; D000818:Animals; D002245:Carbon Dioxide; D019343:Citric Acid; D004247:DNA / Q000008:administration & dosage; D016503:Drug Delivery Systems; D004355:Drug Stability; D004365:Drugs, Chinese Herbal; D015316:Genetic Therapy; D006801:Humans; D001239:Inhalation; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008156:Luciferases / Q000378:metabolism; D008168:Lung / Q000201:enzymology / Q000378:metabolism*; D008353:Mannitol; D051379:Mice; D008970:Molecular Weight; D011208:Powders
D004365:Drugs, Chinese Herbal; D007328:Insulin; D011208:Powders; C120250:choto-san; D002245:Carbon Dioxide; D019343:Citric Acid; D008353:Mannitol; D004247:DNA; D008156:Luciferases