Ibuprofen, indomethacin and diclofenac sodium nanoaerosol: Generation, inhalation delivery and biological effects in mice and rats

•Nanoaerosol formation, pulmonary delivery and anti-inflammatory/analgesic effect are studied for the nonsteroidal anti-inflammatory drugs (indomethacin, ibuprofen and sodium diclofenac) in mice and rats.•The bioavailability for pulmonary delivered drugs is 10,000 times higher than for the case of oral administration.•The lung permeability for ibuprofen decreases during inhalation from about 100% initially to 1% after 60 min of inhalation; however, the lung permeability is restored completely after 24 h of recovery.

Nanoaerosol formation and pulmonary delivery are studied for the nonsteroidal anti-inflammatory drugs (NSAIDs) indomethacin, ibuprofen and sodium diclofenac in mice and rats. Nanoaerosol is generated by the evaporation-nucleation technique in a flow chamber. Aerosol concentrations and mean diameters are within the ranges 105−3·107 cm−3 and 4-200 nm, respectively. The NSAIDs biological action (analgesic and anti-inflammatory) for pulmonary delivery is found to be the same as that for oral delivery with the inhalation dose four to five orders of magnitude less than the orally delivered one. To clarify the mechanism of NSAIDs to blood absorption and elimination, the pharmacokinetics of ibuprofen is studied in rats. The permeability Plung of lung epithelium (the ratio between blood absorption and lung deposition rates) is determined. It is found that the quantity Plung is a function of inhalation time decreasing from about 100% initially to 1% after 60 min of inhalation. However, lung permeability is restored completely after 24 h of recovery. Histologic analysis shows that the reason of a decrease in pulmonary bioavailability is in reversible lung changes like the goblet cells secretion, and vascular and capillary hyperemia.

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