| Abstract | Tricyclic antidepressants (TCAs) have potent local pain blockade properties that could be of interest in relieving chronic pain states as neuropathic pain. The aim of this work was to reach a persistent control of nociceptive and neuropathic pain by means of an in- jectable controlled release system using lower than usual doses of TCAs. To address this issue, amitriptyline, doxepin and imipramine were encapsulated with poly (lactic-co-glycolic) acid (PLGA) as polymer. Nanoparticles were characterized. The in vitro drug release profile and mechanism was evaluated, and the in vivo analgesic and anti-allodynic activity in front of heat-induced nociceptive pain and sciatic nerve chronic constriction injury, respectively, was tested. The mean±SD particle size and drug loadings (%) of the nanoparticles obtained were 420±13, 480±73 and 373±25nm, and 40.46±4.11, 31.09±3.02 and 32.20±3.20% for amitriptyline, doxepin and imi- pramine, respectively. According to the Korsmeyer-Peppas model, the release mechanism of doxepin was diffusion controlled, while a combination of Fickian diffusion and polymer relaxation/erosion of the PLGA matrix was involved for amitriptyline and imipramine. Af- ter local infiltration of nanoparticles in rats, the antinociceptive and anti-allodynic activity of the encapsulated drugs were long-lasting and higher than that observed from the solutions. Amitriptyline elicited the lower analgesic effect. Doxepin showed the most outstanding results and its encapsulation led to a 62% and 229% increase in antinociceptive and anti-allodynic activity, respectively. So, this drug could be considered as a therapeutical alternative in pain relieving treatments.© 2011 Bentham Science Publishers Ltd. |
