O-carboxymethyl chitosan-grafted-cholesterol succinic acid monoester nanomicelles improve oral absorption of cannabidiol: Preparation, intestinal absorption in vitro, and pharmacokinetics in vivo

Cannabidiol (CBD) is a natural cannabinoid with anti-epileptic, anti-inflammatory, and other biological activities. However, CBD is highly lipophilic, and its oral bioavailability is only 6%, which greatly limits its efficacy. Here, we aimed to overcome the poor solubility and low oral bioavailability of CBD by formulating O-carboxymethyl chitosan-grafted cholesterol succinate monoester-loaded cannabidiol nanomicelles (CBD/CCMC NMs). The particle size, polydispersity index, and zeta potential of the optimised CBD/CCMC NMs were 230.61 ± 1.82 nm, 0.17 ± 0.05, and -13.52 ± 1.24 mV, respectively. And it showed a spherical structure under scanning electron microscopy, exhibited stability at 25 °C and 37 °C, with pH-dependent release in vitro . There was improved the solubility of CBD in water by 568.67-fold and exhibited excellent biocompatibility. There was also improved bioavailability of CBD. Therefore, CBD/CCMC NMs can be used as delivery systems for improving the solubility and intestinal absorption of hydrophobic drugs.