Aerosolized liposomes with dipalmitoyl phosphatidylcholine enhance pulmonary insulin delivery.
The pulmonary insulin delivery characteristics of liposomes were examined. Aerosolized liposomes containing insulin were administered into rat lungs and the enhancing effect on insulin delivery was evaluated by changes of plasma glucose levels. Liposomes with dipalmitoyl phosphatidylcholine (DPPC) enhanced pulmonary insulin delivery in rats, however, liposomes with dilauroyl, dimyristoyl, distearoyl or dioleoyl phosphatidylcholine did not. Liposomes with DPPC also enhanced the in vitro permeation of FITC dextran (Mw 4400, FD-4) through the calu-3 cell monolayer by reducing the transepithelial electrical resistance and did not harm lung tissues in rats. These findings suggest that liposomes with DPPC enhance pulmonary insulin delivery by opening the epithelial cell space in the pulmonary mucosa not mucosal cell damage. Liposomes with DPPC could be useful as a pulmonary delivery system for peptide and protein drugs.
Department of Pharmaceutics, Graduate School of Pharmaceutical Sciences, Hokkaido Pharmaceutical University, 7-1 Katsuraoka-cho, Otaru-city 047-0264, Japan. s-chono@hokuyakudai.ac.jp
Sumio
S
Chono
Rie
R
Fukuchi
Toshinobu
T
Seki
Kazuhiro
K
Morimoto
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D000818:Animals; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D002463:Cell Membrane Permeability; D003911:Dextrans / Q000008:administration & dosage / Q000493:pharmacokinetics; D004847:Epithelial Cells / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D008264:Macrophages / Q000378:metabolism; D008297:Male; D010316:Particle Size; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D003911:Dextrans; D007328:Insulin; D008081:Liposomes; D015060:1,2-Dipalmitoylphosphatidylcholine; D007770:L-Lactate Dehydrogenase; D016650:Fluorescein-5-isothiocyanate