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. METHOD: 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.

Anti-inflammatory effect from indomethacin nanoparticles inhaled by male mice.

The respiratory system provides entry for drug nanoparticles to cure systemic diseases. The modern devices that are available on the market of therapeutic aerosol delivery systems have a number of disadvantages. There remains a need for an alternative means that is low cost, convenient, and capable of producing small-sized particles. On the other hand, one-third of the modern drugs are poorly water soluble. Many currently available injectable formulations of such drugs can cause side effects that originate from detergents and other agents used for their solubilization. The aerosol lung administration may by a good way for delivery of the water-insoluble drugs. We present here a new way for the generation of drug nanoparticles suitable for many water insoluble substances based on the evaporation-condensation route. In this paper the indomethacin nanoaerosol formation was studied and its anti-inflammatory effect to the outbred male mice was examined. The evaporation-condensation aerosol generator consisted of a horizontal cylindrical quartz tube with an outer heater. Argon flow was supplied to the inlet and the aerosol was formed at the outlet. The particle mean diameter and number concentration were varied in the ranges 3 to 200 nm and 10(3) to 10(7) cm(-3), respectively. The liquid chromatography and X-ray diffraction methods have shown the nanoparticles consist of the amorphous phase indomethacin. The aerosol lung administration experiments were carried out in the whole-body exposure chamber. Both the lung deposited dose and the particle deposition efficiency were determined as a function of the mean particle diameter for mice being housed into the nose-only exposure chambers. The anti-inflammatory action and side pulmonary effects caused by the inhalation of indomethacin nanoparticles were investigated. It was found that the aerosol administration was much more effective than the peroral treatment. The aerosol route required a therapeutic dose six orders of magnitude less than that for peroral administration.