Abstract
Abstract Cannabidiol (CBD) is a promising pharmaceutical agent to treat pain, inflammation, and seizures without the psychoactive effects of delta-9-tetrahydrocannabinol (THC). While CBD is highly lipophilic and can cross the blood-brain barrier (BBB), its bioavailability is limited and clearance is quick, limiting its effectiveness in the brain. To improve its effectiveness, we developed a unique nanoformulation consisting of CBD encapsulated within the biodegradable and biocompatible polymer, methoxy polyethylene glycol-poly(lactic-co-glycolic acid) (mPEG-PLGA). mPEG-PLGA-CBD nanoparticles exhibited negligible cytotoxicity over a range of concentrations in CCK-8 assays performed in human astrocytes and brain microvascular endothelial cells. Furthermore, in an in-vitro BBB model, they exhibited rapid BBB permeability without harming BBB integrity. An in vivo Chronic Constriction Injury animal pain model was employed to study the efficacy of mPEG-PLGA-CBD in doses 1, 3 and 10 mg/kg, and it was found that 45–55 nm CBD nanoparticles with an encapsulation efficiency of 65 % can cross the BBB. Additionally, 3 and 10 mg/kg mPEG-PLGA-CBD nanoformulation provided prolonged analgesia in rats on day 2 and -4 post-injection, which we propose is attributed to the sustained and controlled release of CBD. Future studies are required to understand the pharmacokinetics of this nanoformulation.
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