Pulsating aerosols for drug delivery to the sinuses in healthy volunteers.
OBJECTIVE
Approximately 10 to 15 percent of the European and U.S. population have chronic rhinosinusitis, but effective treatment remains a challenge. There has been limited success using topical drug delivery to the nose and the paranasal cavities/sinuses, in part because most nasally administered aerosol drug formulations are efficiently filtered at the nasal valve and fail to reach the osteomeatal area and sinuses.


METHODS
Feasibility study.


METHODS
Nuclear medicine department.


METHODS
Pulsating airflows were applied to the nasal cavity and sinus ventilation was studied in five healthy human volunteers using dynamic (81m)Kr-gas gamma camera imaging. Furthermore, deposition and retention of (99m)Tc-DTPA radiolabeled aerosols delivered by nasal pump sprays or by pulsating aerosols was assessed in each volunteer over a 24-hour period.


RESULTS
Only the pulsating airflow demonstrated efficient (81m)Kr-gas ventilation of the paranasal sinuses. No drug was deposited into the sinuses using nasal pump sprays, but up to 6.5 percent of the nasally administered drug was deposited into the sinuses using pulsating airflow. Clearance kinetics of the drug was reduced after pulsating aerosol delivery compared to nasal pump sprays. Residence time of the drug at the site of deposition was up to three-fold longer with pulsating aerosol delivery than with nasal pump sprays.


CONCLUSIONS
Our data support the hypothesis that topical drug delivery in relevant quantities to the nose and osteomeatal areas, including the paranasal sinuses, is possible using pulsating airflows. Furthermore, the frequency of drug applications may be reduced due to a delayed clearance and longer residence time.
Möller
Winfried
W
Institute for Lung Biology and Disease, Helmholtz Zentrum München-German Research Center for Environmental Health, Gauting, Germany. moeller@helmholtz-muenchen.de
Schuschnig
Uwe
U
Khadem Saba
Gülnaz
G
Meyer
Gabriele
G
Junge-Hülsing
Bernhard
B
Keller
Manfred
M
Häussinger
Karl
K
D000281:Administration, Intranasal; D000328:Adult; D000336:Aerosols / Q000008:administration & dosage*; D002908:Chronic Disease; D005240:Feasibility Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009296:Nasal Cavity / Q000000981:diagnostic imaging*; D009330:Nebulizers and Vaporizers; D010256:Paranasal Sinuses / Q000000981:diagnostic imaging*; D004369:Pentetic Acid; D011877:Radionuclide Imaging; D016284:Technetium Tc 99m Pentetate / Q000008:administration & dosage
D000336:Aerosols; D004369:Pentetic Acid; D016284:Technetium Tc 99m Pentetate