Enhanced bioavailability and biosafety of cannabidiol nanomicelles for effective anti-inflammatory therapy

Cannabidiol(CBD)shows great anti-inflammatory potential;however,the hydrophobicity and strong first-pass effect of CBD leads to its extremely low oral bioavailability.Poloxamer 407(P407)is a tri-block copolymer composed of(poly)ethylene oxide(PEO)and(poly)propylene oxide(PPO)sections.It has a PEO-PPO-PEO structure,which is widely used in the preparation of drug delivery systems that are highly biocompatible.When it reaches a certain concentration in water,P407 can self-assemble into a micelle structure containing a hydrophobic core and a hydrophilic shell.A potential approach to enhanc-ing the oral bioavailability of hydrophobic drugs incorporating them into the hydrophilic carrier.We prepared CBD nanomicelles with a drug loading of 14.29%by a cosolvent evaporation method using P407 with appropriate antioxidants.Cell experiments indicated that anti-inflammatory markers(IL-4 and IL-10)increased,while inflammatory markers(TNF-αand IL-6)decreased.Moreover,animal experiments showed that inflammatory cells were inhibited by CBD nanomicelles,and the anti-inflammatory effect of micelles was better than that of CBD,while no obvious evidence indicated toxicity to the liver and kidney.