Study on Tissue Distribution of Apigenin Nanosuspension in Mice / 中国药房

ABSTRACT

OBJECTIVE：To study the distri bution and targeting characteristics of Apigenin nanosuspension （AP-NPs）in mice. METHODS：AP-NPs was prepared with ultrasound microprecipitation. Kunming mice were randomly divided into apigenin （AP） solution group and AP-NPs suspension group ，with 45 mice in each group. The mice were given relevant medicine intragastrically （80 mg/kg）；blood sample of eyeball 500 μL were collected before medication（0 h）and 0.25，0.5，1，2，4，6，8，10 h after medication. After the last blood collection ，the mice were sacrificed and their heart ，liver，spleen，lung，kidney and brain tissues were taken. After protein precipitation with methanol ，HPLC method was adopted for determining plasma and tissues. The determination was performed on Shimadzu ODS-SP column with mobile phase consisted of methanol-water （70 ∶ 30，V/V）at the flow rate of 1.0 mL/min. The detection wavelength was set at 340 nm，and column temperature was 35 ℃. The sample size was 20 μL. The concentration of AP in different samples was calculated according to standard curve，main pharmacokinetic parameters （AUC，cmax）of AP and the ratio of peak concentration （ce），relative uptake rate （RUE），uptake ratio and its change value were calculated with DAS 2.0 software and Excel 2010 software；the tissue distribution and targeting characteristics of AP were analyzed. RESULTS：The linear range of AP in plasma and tissue s were 0.1-25.0 μg/mL（all r＞0.99）；the lower limits of quantification were 0.1 μg/mL. RSDs of intra-day and inter-day were all lower than 15％，and the accuracy were 94.37％-117.48％. The extraction recovery rates were all more than 80％. Compared with AP solution group ，the concentrations of AP in plasma sample （during 0.5-6 h），liver tissue （during 0.25-8 h），spleen tissue （during 0.25-8 h）and cerebral tissue （during 0.25-4 h）were increased significantly in AP-NPs suspension group （P＜0.05 or P＜0.01），and the highest in liver tissue. The concentrations of AP in heart tiusse （6 h），liver tissue （10 h），lung tissue （0.5 h），spleen tissue （during 0.25-10 h）were decreased significantly （P＜ 0.05 or P＜0.01）. There was statistical significance in AUC and cmax of AP in plasma and tissue samples between 2 groups（P＜ 0.05）. The ce，RUE，uptake ratio and its change value of liver tissue were the highest ，being 1.34±0.40，1.99±0.29，48.49％ and 15.71％ . CONCLUSIONS ：After AP is made into nanosus- pension，the distribution of drug tissue is changed ，especially targeting effect on liver tissue is improved.