Nanochannel delivery system for CBD: Sustained low level plasma levels without liver toxicity

Abstract

Cannabidiol (CBD) is a plant-derived cannabinoid found in marijuana and hemp that has been intensely investigated for its putative anti-inflammatory, anxiolytic and/or analgesic effects. Since all these conditions require long-term treatment, sustained release formulations are being investigated. The nanochannel delivery system (nStrada™), an implant device containing 1 mL of CBD formulation in either sesame oil (SES) or medium-chain triglyceride (MCT) vehicles was used in a 35-day sustained-release pharmacokinetic (PK) experiment in female rats. Rats were surgically implanted with either a polyetheretherketone (PEEK) or titanium (Ti) device on day 0 (D0) and blood was obtained several times a week over 35 days. Following the maximum concentration (Cmax) at D1 of 74.3 ± 26.9 ng/mL and 26.3 ± 16.5 ng/mL in MCT and SES, respectively, the subcutaneous release of CBD from the nStrada™ implants exhibited sustained in vivo release kinetics by D14 until termination of the study on D35. The average steady-state levels were 0.8 ng/mL for CBD delivered in MCT and 0.4 ng/mL for CBD delivered in SES. At necropsy on D35, serum alanine aminotransferase (ALT) was determined, and liver histopathology was evaluated, and neither revealed liver toxicity. Skin histopathology surrounding the implanted devices revealed changes consistent with fibrosis as expected. In vitro release data confirmed consistent delivery of CBD into media containing phosphate buffered saline (PBS) with 5% Labrasol. Overall, these results provide a pre-clinical evaluation of CBD PK following implantation of a constant release device over 35 days and confirm at these CBD plasma levels, there is no concern for liver toxicity.