Objective: To compare the difference on the bioavailability between cannabidiol (CBD)-loaded flexible zein nanoparticles (FZP-CBD) and CBD-loaded natural zein nanoparticles (NZP-CBD) by investigating the pharmacokinetics of both in normal rats. Methods: FZP-CBD and NZP-CBD were prepared by inverse-solvent method. SD rats were administrated with two groups of nano-preparations (the low, medium and high doses of CBD were 20, 50 and 100 mg·kg-1, respectively) by intragastric administration. Blood samples were collected from orbital venous plexus before and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 h after administration. The concentrations of CBD were determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS), using Waters Atlantis T3 (100 mm×2.1 mm,3 μm) column, 0.1% formic acid-water as mobile phase A, 0.1% formic acid-acetonitrile as mobile phase B, gradient elution, at a flow rate of 0.3 mL·min-1, the column temperature was 30 ℃ and the injection volume was 1 μL. The detection was carried out by electrospray ionization source (ESI), positive ion mode scanning and multiple reaction monitoring (MRM) mode. Winnonlin 8.1 software was used to calculate the pharmacokinetic parameters. Results: The Cmax of low, medium and high concentration of FZP-CBD and NZP-CBD were (414.8±184.1) μg·L-1, ( 715.3±191.7) μg·L-1, (1 798.4±854.5) μg·L-1 and (240.6±143.8) μg·L-1, (542.3±235.4) μg·L-1, (1 173.3±317.0) μg·L-1, respectively. AUC0-t were (1 955.2±632.9) μg·h·L-1, (7 255.2±1 573.8) μg·h·L-1, (26 634.0±16 479.7) μg·h·L-1 and (1 438.6±557.1) μg·h·L-1, (6 316.5±2 916.3) μg·h·L-1, (15 674.1±4 365.7) μg·h·L-1, respectively. Compared with NZP-CBD, the Cmax of low, medium and high concentration of FZP-CBD increased by 1.7, 1.3 and 1.5 times respectively, and AUC0-t increased by 1.4, 1.1 and 1.7 times respectively, bioavailability(F) increased by 135.9%, 114.9%, 169.6% respectively. Conclusion: The specificity and sensitivity of LC-MS assay can satisfy the pharmacokinetic determination of rat serum. Compared with NZP-CBD, FZP-CBD prepared by acid modification can improve CBD bioavailability. This study can improve the utilization value of CBD and provide a new idea for the application of CBD in the area of medicine and pharmacy.
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