The Brain Release Characteristics Of Intranasal Administration Of Resveratrol

Objective: To provide experimental evidences to the application of resveratrol in brain diseases, resveratrol loaded hydroxypropyl-β-Cyclodextrin(HP-β-CD) inclusion complex was fabricated and the brain release characteristics of drug were preliminary characterized after I.Vand nasal administration of resveratrol in rabbits.Methods: Physicochemical properties of resveratrol were determined by phase equilibrium method, shake-flask method and the stress test. In vitro permeation test was performed using vertical Franz diffusion cell to observe the effect of hydroxypropyl-β-cyclodextrin on the penetration resveratrol through the fresh porcine nasal mucosa. Resveratrol-hydroxypropyl-β-cyclodextrin inclusion complex were prepared using freeze-drying method, and confirmed through Ultraviolet spectroscopy, FT-IR and X-ray diffraction method. The distributions of resveratrol in brain area were compared after intravenous injection and nasal perfusion of resveratrol-hydroxypropyl-β-cyclodextrin inclusion complex in rabbits, including blood, cerebrum, rhinencephalon and turbinate.Results: Resveratrol was showed varying degrees instability in different p H condition and sensitive to oxidation and strong light environment. The partition coefficient of resveratrol in octanol /water system was 3.09±0.3. The results of in vitro permeation test showed that hydroxypropyl-β-cyclodextriworked(HP-β-CD) played the most effective enhancing roles compared with chitosan and lecithin. Both of the assay results of FT-IR and X-ray diffraction indicated the formation of resveratrol loaded HP-β-CD inclusion complex(Res-HP-β-CD) after freeze-drying method. The distribution of resveratrol showed similar properties in blood, cerebrum and rhinencephalon after i.v injection and nasal perfusion of Res-HP-β-CD in rabbits, while the significant high turbinates drug concentration in latter case. This might be domenstrate indirectly the exsitance of penetrating pathway of drug through nasal mocosa into the brain.Conclusion: The solubility and stability of resveratrol could be improved through the formation of hydroxypropyl-β- cyclodextrin inclusion complex. Subsequently, the absorption and distribution in brain site of resveratorol were also could be increased through nasal mucosa administration of HP-β- CD inclusion complex. In a word, the brain specific delivery of resveratorol is feasible through nasal mucosa administration.