TitleTricyclic Antidepressants-loaded Biodegradable PLGA Nanoparticles: In Vitro Characterization and In Vivo Analgesic and Anti-Allodynic Effect
Publication TypeJournal Article
Year of Publication2011
AuthorsGarcia X, Escribano E, Colom H, Domenech J, Queralt J
JournalCurrent Nanoscience
Date Publishedjun
KeywordsAnti-allodynia, Antinociception, In vitro release, Korsmeyer-peppas, Plga nanoparticles, Tricyclic antidepressants
AbstractTricyclic 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.