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 injectable 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 imipramine, 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. After 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.
Keywords: Anti-allodynia, antinociception, in vitro release, Korsmeyer-Peppas, PLGA nanoparticles, tricyclic antidepressants, Gold nanaoparticle, Multi-functionalized gold nanoparticles, Nitrite, Detection, Electrochemistry, Cyclic voltammetry, Electrochemical impedance spectroscopy, DNA, Griess reaction, hexaammineruthenium(III) chloride, thiolated oligonucleotides, chemically modified electrode, surface modification
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