The effects of intrathecal morphine encapsulated in L- and D-dipalmitoylphosphatidyl choline liposomes on acute nociception in rats

Liposomes can serve as a sustained-release carrier system, permitting the s pinal delivery of large opioid doses restricting the dose for acute systemi c uptake. We evaluated the antinociceptive effects of morphine encapsulated in liposomes of two isomeric phospholipids, L-dipalmitoylphosphatidyl chol ine (L-DPPC) and D-dipalmitoylphosphatidyl choline (D-DPPC), in comparison with morphine in saline. Sprague-Dawley rats with chronic lumbar intratheca l catheters were tested for their acute nociceptive response using a hindpa w thermal escape test. Their general behavior, motor function, pinna reflex , and corneal reflex were also examined. The duration of antinociception wa s longer in both liposomal morphine groups than in the free morphine group. The peak antinociceptive effects were observed within 30 min after intrath ecal morphine, L-DPPC or D-DPPC morphine injection. The rank order of the a rea under the effect-time curve for antinociception was L-DPPC morphine > D -DPPC morphine > morphine. The 50% effective dose was: 2.7 mu g (morphine), 4.6 mu g (L-DPPC morphine), and 6.4 mu g (D-DPPC morphine). D-DPPC morphin e had less side effects for a given antinociceptive AUC than morphine. In c onclusion, L-DPPC and D-DPPC liposome encapsulation of morphine prolonged t he antinociceptive effect on acute thermal stimulation and could decrease s ide effects, compared with morphine alone.