Extract-phospholipid Complex: Preparation and Initial Pharmacodynamics Research in Rats

Background: Baicalin, a flavonoid glycoside compound present in Scutellaria baicalensis, has shown a wide spectrum of biological activities, but its liposolubility, water-solubility and mucosal permeability are all very poor, which leads to the low concentration in brain and poor bioavailability by oral or intravenous injective administration.

Objective: The primary objective of this study was to formulate the Scutellaria baicalensis extract (SBE) with phospholipid to yield Scutellaria baicalensis extract-phospholipid complex (SBEPC) , and to evaluate its pharmacodynamics in the middle cerebral artery occlusion (MCAO).

Methods: The optimal preparation technology of SBEPC was obtained through single-factor test and central composite design-response surface methodology (CCD-RSM), and was characterized with various analytical techniques including SEM, FT-IR and NMR. The storage conditions of SBEPC were established through stability study and the MCAO rat model was investigated through conducting pharmacodynamic studies to screen the appropriate administration and dose of SBEPC as well as to verify the neuroprotective effect of SBEPC on cerebral ischemia-reperfusion injury.

Results: The optimized preparation conditions of SBEPC were summarized as follows: the ratio of phospholipids to drug was 2:1, the drug concentration was 3.5 mg/ml, the reaction temperature was 50 °C, and the entrapment efficiency was over 93.00%. Stability studies have demonstrated that SBEPC should be stored under 40 °C in a dry and ventilated place away from light and below 37% humidity. Furthermore, pharmacodynamic studies have found that, compared with SBE, SBEPC could introduce drugs into the brain and better exert the neuroprotective effect on MCAO rats, and the optimal administration and dose concentration of SBEPC were nasal administration and 40 mg/ml, respectively.

Conclusion: These findings demonstrate that SBEPC is successfully prepared by CCD-RSM. SBEPC can enhance drugs' ability to enter the brain and improve the bioavailability of drugs in brain, and can effectively exert the neuroprotective effect on cerebral ischemia-reperfusion injury as compared with SBE.