[Evaluation of brain-targeted trendence of scutellarin nasal administration]

To evaluate the feasibility of developing brain-targeted nasal delivery system of scutellarin by the passage between nase and brain in nasal olfactory area.

The samples of cerebrospinal fluid (CSF) and blood were prepared by cranial puncture and femoral artery catheterization methods respectively according to the certain sampling time after drug administered. The scuteIlarin concentration of samples were determined by 125 marked method. Pharmacokinetic parameters were calculated by trapezoidal rule. The brain-targeted trendence were evaluated by the value of the index AUC(brain)/AUC(plasma).

The distribution of scutellarin in brain following intranasal administration was different between tissues. Drug concentration in olfactory bulb achieved to peak at 5-15 min after intranasal administration, while in brain tissue was 30-60 min. Above all, peak concentration in olfactory bulb and olfactory region respectively were (574.8 +/- 205.), (323.4 +/- 128.3) ng x g(-10, both are higher than CSF, which is (123.2 +/- 29.3) ng x g(-1). Moreover, the distribution of scutellarin given by intranasally in brain was: olfactory bulb (OB) >> olfactory region (OR) > cerebrospinal fluid (CSF) > cerebellum(CB) > medulla oblongata (MO) > cerebrum (CR); AUC(0-240) of olfactory bulb, olfactory region and CSF after scutellarin intranasal administration were 5.54, 5.07 and 5.51 times of that after intravenous injection, respectively. And the AUC(0-240) of other brain tissues after intranasal administration were also higher than that after intravenous injection. AUC(brain tissue)/ AUC(plasma) of every brain tissues by intranasally are all higher than that by intravenously remarkably. For instance, 5 min after intranasal administration, the value of AUC(CSF)/ AUC(plasma), AUC(OB)/AUC(plasma), and AUC(CR)/AUC(plasma) were 30.34, 56.93, and 6.14 times of that by intravenously.

Part of scutellarin could be straightly transported into brain by the intranasal administration. Its absorption pathway was: the molecule of Scutellarin throughed olfactory mucosa in nasal cavity into olfactory bulb in arachno-hypostegal cavity, and then entered into olfactory region, CSF, cerebrum and cerebellum gradually. It showed that olfactory bulb was the only way for drug molecule to go through nasal cavity into brain. It had a significant trendence of brain-targeted when compared to oral administration and intravenous injection, which indicated a certain feasibility to develop a brain-targeted nasal delivery system for scutellarin.