Biovector nanoparticles improve antinociceptive efficacy of nasal morphine.
OBJECTIVE
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.
Betbeder
D
D
Biovector Therapeutics SA, Chemin du Chebe Vert BP 169, Labege, France. didier.betbeder@biovector.com
Spérandio
S
S
Latapie
J P
JP
de Nadai
J
J
Etienne
A
A
Zajac
J M
JM
Francés
B
B
D000281:Administration, Intranasal; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001682:Biological Availability; D004337:Drug Carriers; D008297:Male; D051379:Mice; D008863:Microspheres; D009020:Morphine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*
D000701:Analgesics, Opioid; D004337:Drug Carriers; D009020:Morphine