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Biovector nanoparticles improve antinociceptive efficacy of nasal morphine
D Betbeder1, S Spérandio, J P Latapie
1Biovector Therapeutics SA, Chemin du Chebe Vert BP 169, Labege, France. didier.betbeder@biovector.com
Purpose:
We have studied the antinociceptive activity and blood and brain delivery of nasal morphine with or without Biovector nanoparticles in mice.
Methods:
A tail flick assay was used to evaluate the antinociceptive activity. The kinetics of morphine were evaluated in blood and brain, using tritiated morphine as tracer.
Results:
These nanoparticles were shown to increase the duration of the antinociceptive activity of morphine after nasal administration. This effect was not due to an increase of morphine in the blood; and the analgesic activity of morphine in association with nanoparticles was reversed by naloxone. The ED50 value was 33.6+/-15.6 mg/kg for morphine alone and 14.4+/-7.6 mg/kg in presence of nanoparticles. They were only effective at low doses (1.5 to 2.5 microg), a higher or a lower dose had no effect. No interaction was found between nanoparticles and morphine. NaDOC, a permeation enhancer, was unable to improve nasal morphine activity.
Conclusions:
These results show the presence of nanoparticles only at a very specific dose increases the antinociceptive activity of nasal morphine in mice. The occurrence of a direct transport of morphine from the nasal mucosa to the brain is discussed.