The present study is focused on the development of cannabidiol-loaded polymeric nanomicelles as a drug delivery system with neuroprotective effects. Cannabidiol was loaded in Pluronic micelles (Pluronic P123 or its combination with Pluronic F127) possessing an average diameter smaller than 50 nm and high encapsulation efficiency for the hydrophobic drug (80% and 84%, respectively). The successful encapsulation and transformation of cannabidiol in amorphous phase were observed by IR spectroscopy and X-ray diffraction, respectively. Studies with neuroblastoma cells (SH-SY5Y and Neuro-2a) showed that the pure cannabidiol caused a dose-dependent reduction of cell viability, whereas its loading into the micelles decreased cytotoxicity. Further, neuroprotective effects of pure and micellar cannabidiol were examined in a model of H2O2-induced oxidative stress in both neuroblastoma cells. The pre-treatment of cell lines with cannabidiol loaded into the mixed Pluronic P123/F127 micelles exerted significantly stronger protection against the oxidative stress compared to pure cannabidiol and cannabidiol in single Pluronic P123 micelles. Interestingly, the empty mixed P123/F127 micelles demonstrated protective activity against the oxidative stress. In conclusion, the study revealed the opportunity to formulate a new drug delivery system of cannabidiol, in particular nanosized micellar aqueous dispersion, that could be considered as a perspective platform for cannabidiol application in neurodegenerative diseases.
Keywords: cannabidiol; nanomicelles; neuroblastoma cells; neuroprotection.