Quantitation of Cannabidiol (CBD) in brain regions and plasma following intranasal administration of a CBD nanoformulation

Abstract Background and objective Delivering therapeutic drugs to the brain for neurological disorders remains challenging due to the restrictive nature of the blood–brain barrier (BBB). Intranasal (IN) nanoparticle delivery may enhance the bioavailability of lipophilic cannabidiol (CBD), addressing limitations associated with systemic administration. Methods Further optimization of nanoparticle properties is necessary to enhance brain uptake and therapeutic potential for neurological disorders. Following IN administration of the nanoformulation, C57BL/6 male mice (3–6 months old, n = 4/group) were euthanized at 2, 4, and 8 h. Plasma, olfactory bulb (OB), hippocampus (HP), striatum (STR), and cortex (CTX) were collected and analyzed for CBD and 7-COOH-CBD using liquid chromatography-mass spectrometry (LC–MS). Two-way analysis of variance with Tukey’s multiple comparisons was used for statistical analysis. Results CBD levels in the brain peaked at 4 h (5788 ng/mg), while 7-COOH-CBD reached its highest concentration at 2 h (3080 ng/mg). In plasma, maximum CBD levels were detected at 4 h (797 µg/mL), whereas 7-COOH-CBD peaked at 2 h (893 µg/mL). Despite measurable brain penetration, only 0.12% of the administered dose reached brain tissue, with 15.94% retained in plasma. Conclusion This is the first study to provide the quantification of CBD and its 7CBD-COOH in various brain regions following IN administration of a CBD nanoformulation. While the approach facilitated brain delivery, overall bioavailability remained low. The use of four mice per group is a limitation that may impact the internal validity of these findings. This study aimed to develop a novel hydrophilic CBD nanoformulation for IN delivery and quantify its distribution and its major metabolite, 7-carboxy-cannabidiol (7CBD-COOH) in distinct brain regions and in plasma of mice.This methodology has the potential to overcome the limits of conventional CBD administration, providing a more effective treatment strategy for targeting brain diseases.