Cannabinoids delivery systems based on supramolecular inclusion complexes and polymeric nanocapsules for treatment of neuropathic pain

• Main Author: Astruc-Diaz, Fanny
• Language: ENG
• Published: Université Claude Bernard - Lyon I 2012
• Subjects: [SDV:MHEP] Life Sciences/Human health and pathology; [SDV:MHEP] Sciences du Vivant/Médecine humaine et pathologie; Cannabinoids; CB2 agonists receptors; Cyclodextrin; Cationic polymeric nanocapsules; Phytocannabinoid
• Online Access: http://tel.archives-ouvertes.fr/tel-00935588; http://tel.archives-ouvertes.fr/docs/00/93/55/88/PDF/TH2012DiazFanny.pdf

Cannabinoids (CBs) and particularly CB2 agonists have been shown to reduce pain andinflammation without eliciting any apparent psychotropic effect conversely to CB1agonist compounds. CBs candidates are usually lipophilic non drug-like compoundswith poor bioavailability. To serve the purpose of evaluating new synthetic CB2 agonistsdeveloped by our group, on in vivo neuropathic pain models, an enabling formulationstrategy has been set up and four Drug Delivery Systems (DDS) developed. Forparenteral administration, cyclodextrin (CD)-based inclusion complexes, liposomes andsurfactants/co-solvents micellar solution have been investigated whereas Self-Emulsifying DDS (SEDDS) was selected for oral administration. A pharmacologicalstudy conducted with lead compound MDA7, formulated in CD-based DDS resulted inthe higher antinociceptive activity. A comprehensive study of the inclusion mechanismof MDA7 in the CD supramolecular complexes prepared was carried out. MDA7pharmacokinetic profile was also generated formulated in micellar solution and SEDDS.Besides, cationic polymeric nanocapsules (NCs) have been designed to serve as aprotective DDS for oral administration of a dietary phytocannabinoid CB2 agonist.Studies were undertaken to characterize and evaluate the influence of differentparameters on NCs formation prepared by nanoprecipitation. The cationic NCsdeveloped have been explored for their property to yield proportion of counterioniccondensation in the presence of macrocycles bearing anionic groups such assulfobutylether-beta-cyclodextrin or to form electrostatic interactions/host-guestcomplexion with cucurbit[n]uril.