Pulmonary distribution and clearance of two beclomethasone liposome formulations in healthy volunteers.
The pulmonary distribution and clearance of 99mTc-labelled beclomethasone dipropionate (Bec) dilauroylphosphatidylcholine (DLPC) and dipalmitoylphosphatidylcholine (DPPC) liposomes were compared in 11 healthy volunteers using gamma scintigraphy. As delivered by using the Aerotech jet nebulizer both liposome aerosols had a suitable droplet size (mass median aerodynamic diameter 1.3 microm) allowing deep pulmonary deposition. However, in the total drug output during the inhalation there was a relatively large difference between DLPC and DPPC of 11.4 and 3.1 microg, respectively. In a gamma camera study no significant differences existed in the central/peripheral lung deposition between the DLPC and DPPC formulations. Progressive clearance of both Tc-labelled Bec liposomes was seen: 24 h after inhalation, 79% of the originally deposited radioactivity of DLPC liposomes and 83% of that of DPPC liposomes remained in the lungs. Thus there was slightly slower clearance of inhaled liposomes using DPPC instead of DLPC. We conclude that both liposome formulations are suitable for nebulization, although aerosol clouds were more efficiently made from the DLPC liposome suspension. Our results support the view that liposome encapsulation of a drug can offer sustained release and drug action in the lower airways.
Saari
M
M
Department of Pulmonary Diseases, Tampere University Hospital, FIN-36280, Pikonlinna, Finland. marisanna.saari@sci.fi
Vidgren
M T
MT
Koskinen
M O
MO
Turjanmaa
V M
VM
Nieminen
M M
MM
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000008:administration & dosage / Q000493:pharmacokinetics; D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D001507:Beclomethasone / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004337:Drug Carriers; D005260:Female; D006801:Humans; D008081:Liposomes; D008168:Lung / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D015609:Organotechnetium Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics; D010316:Particle Size; D010713:Phosphatidylcholines / Q000008:administration & dosage / Q000493:pharmacokinetics; D013667:Technetium; D014018:Tissue Distribution
D000336:Aerosols; D018927:Anti-Asthmatic Agents; D004337:Drug Carriers; D008081:Liposomes; D015609:Organotechnetium Compounds; D010713:Phosphatidylcholines; C015153:1,2-dilauroylphosphatidylcholine; D015060:1,2-Dipalmitoylphosphatidylcholine; D013667:Technetium; D001507:Beclomethasone