ABSTRACT
OBJECTIVE：To study the pharmacokinetics and tissue distribution characteristics of Hydroxycamptothecin （HCPT） nanoparticles in rats ，and to investigate their targeting. METHODS ：Male SD rats were randomly divided into 2 groups，with 6 rats in each group. They were given HCPT nanoparticles and HCPT injection （4 mg/kg based on HCPT ）via tail vein respectively. 500 μL fundus venous plexus blood were sampled at 5，30，60，120，240，360，480，600 and 720 min after administration. The plasma concentration of HCPT in rats were measured by HPLC at different time points. The pharmacokinetic parameters were calculated by DAS 3.0 software. Male SD rats were randomly divided into two groups ，with 24 rats in each group. They were given HCPT nanoparticles and HCPT injection （0.6 mg/kg based on HCPT ）via tail vein ，respectively. Blood was immediately taken from the abdominal aorta ，and heart ，liver，spleen，lung，kidney and brain were removed at 30，60，120，240 min after administration. The plasma and tissue concentration of HCPT in rats were measured by HPLC. The distribution of HCPT ineach tissue and targeting were investigated. RESULTS ：HCPT nanoparticles and its injection conformed to a two-compartment model in rats. Compared with HCPT injection ，AUC0-720 min andAUC0- ∞ increased by 1.89 and 1.87 times respectively ， MRT0-720 min and MRT 0- ∞ increased by 2.74 and 3.00 times respectively， t1/2 β increased by 2.75 times，with statistical significance（P＜0.05）. At 30 min after administration ，HCPT nanoparticles and HCPT injection had the highest concentration in lung；with the passage of time ，the drug gradually accumulated in the liver and reached the highest concentration at 60 min. The relative liver uptake rate of HCPT nanoparticles was the highest （6.28）. Taking liver ad target organ ，and the targeting efficiencies of it in heart ，spleen，lung，kindey，brain and plasma were higher than those of HCPT injection. The selectivity index of HCPT nanoparticles in heart ，lung（except for 30 min after administration ），kidney，brain and plasma were significantly higher than those of HCPT injection at 30-120 min after administration. CONCLUSIONS ：HCPT nanoparticles extend the half-life of the drug ， increase its plasma concentration ，and prolong its action time in vivo ，with significant liver targeting.
ABSTRACT
Objective To lay the physiological and biochemical basis for establishing and evaluating tree shrews model of human disease. Methods There were 92 Tupaia belangeri chinensis, in which half of them were male,they were allowed to eat nothing for 12 hours, then we sampled heart blood 0.8~1.0 mL without anesthesia and put blood samples into sterilized centrifuge tube for separation and preparation of serum. Olympus AU5400 automatic biochemistry analyzer was used to measure biochemical indexes. Then 1.5~2.0 mL of urine of each tree shrew was collected and put into sterilized centrifuge tube for measuring renal function by using Combi-scan500 urine analyzer. Fianally SPSS statistics software was used to analyse the measured values, and comapared the measured values with the human reference values. Results There were significant differences in myocardial enzymes and some renal function indexes such as lactic dehydrogenase,α- hydroxybutyric, acid dehydrogenase, creatinine, uric acid, urine specific gravity and pH value between male and female Tupaia belangeri chinensis ( 0.05) . Then determination value of Tupaia belangeri chinensis, male’s and female’s, myocardial enzyme and part of the renal function indexes were compared with the human reference values. Some indexes including urea, urine specific gravity, urine, urobilinogen were in the range of human reference value, while the values of urine bilirubin, urine nitrite. lactate dehydrogenase, creatine kinase, α-hydroxybutyrate dehydrogenase, creatine kinase isoenzyme CKMB were higher than the human reference value. White blood cell, urine protein, ketone, occult blood most of them were negative as the same to human reference value, but sometimes were positive, and the positive rates respectively were 3.95%and 46.1%,39.5%,2.63%. The measured value of Vitamin C was positive that is completely opposite to human reference value, but sometimes is negative, the negative rate was 6.6%. Conclusion Urea, urine specific gravity, urine, urobilinogen, urine bilirubin, urine nitrite can be directly used as the indexes for evaluating tree shrews models of human disease, other indexes can be used as indexes for judgment of the normal physiological and biochemical basis of tree shrews.