Analgesic effect from Ibuprofen nanoparticles inhaled by male mice.
BACKGROUND
Aerosol lung administration is a convenient way to deliver water-insoluble or poorly soluble drugs, provided that small-sized particles are generated. Here, for the outbred male mice, we show that the pulmonary administration of ibuprofen nanoparticles requires a dose that is three to five orders of magnitude less than that for the orally delivered particles at the same analgesic effect.


METHODS
The aerosol evaporation-condensation generator consisted of a horizontal cylindrical quartz tube with an outer heater. Argon flow was supplied to the inlet and aerosol was formed at the outlet. The particle mean diameter and number concentration varied from 10 to 100 nm and 10(3)-10(7) cm(-)3, respectively. The analgesic action and side pulmonary effects caused by the inhalation of ibuprofen nanoparticles were investigated.


RESULTS
The chemical composition of aerosol particles was shown to be identical with the maternal drug. Using the nose-only exposure chambers, the mice lung deposition efficiency was evaluated as a function of the particle diameter.


CONCLUSIONS
The dose-dependent analgesic effect of aerosolized ibuprofen was studied in comparison with the oral treatment. It was found that the dose for aerosol treatment is three to five orders of magnitude less than that required for oral treatment at the same analgesic effect. Accompanying effects were moderate venous hyperemia and some emphysematous signs.
Onischuk
Andrei A
AA
Institute of Chemical Kinetics & Combustion, RAS, Novosibirsk, Russia. onischuk@kinetics.nsc.ru
Tolstikova
Tatyana G
TG
Sorokina
Irina V
IV
Zhukova
Natalya A
NA
Baklanov
Anatoly M
AM
Karasev
Vladimir V
VV
Borovkova
Olga V
OV
Dultseva
Galina G
GG
Boldyrev
Vladimir V
VV
Fomin
Vasilii M
VM
D000280:Administration, Inhalation; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007052:Ibuprofen / Q000008:administration & dosage / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage*; D010316:Particle Size
D018712:Analgesics, Non-Narcotic; D007052:Ibuprofen