Oral non-steroidal anti inflammatory drugs (NSAIDs) are not an effective treatment of Alzheimers disease, because the brain dose is too low. Nasal delivery of NSAIDs such as ibuprofen, flurbiprofen, indomethacin, diclofenac, or naproxen, which inhibit the enzymes cyclooxygenase-1 (cox-1) and cox-2, are used to prevent and/or treat Alzheimers disease, a low grade brain inflammation. The large amount of nasal NSAIDs (e.g., ibuprofen, flurbiprofen, indomethacin, diclofenac, or naproxen) that reaches the brain far exceeds that from an oral dose. Low-molecular-weight lipophilic drugs, such as ibuprofen, naproxen, indomethacin, diclofenac, and flurbiprofen, are readily absorbed into the brain by the intranasal route. Alzheimers starts in the entorhinal cortex, which is closely connected to the olfactory nerves, and spreads anatomically in a defined pattern. Therefore, a nasal NSAID would readily reach the region of the brain where it acts therapeutically.
