Therapautic Effects Of Hydroxycamptothec Nanoparticles Injection On Mice Hepatocarcinoma In Vivo

Objective:To investigate the role to the liver cancer of the nano-modified hydroxycamptothecin(HCPT), the drug concentrations of the liver, liver tumors and blood of mices were determined, which were injected from vein of injection-type HCPT and nano-HCPT.METHODS:①According to the method of High-performance liquid chromatography (HPLC), the HCPT drug content in plasma, liver tissue and liver tumor of mice was tested. Chromatographic conditions:UV-high performance liquid chromatography,384nm of detection wavelength, C18 (250mm×4.6mmID, 10μm) of column, methanol of mobile phase was 10mmol·L-1 phosphate buffer solution= 50:50, pH=3, 1.0ml/min of flow rate, column temperature of 30℃. Orthotopic liver tumor model in mice 50,20 of which were randomly divided into two groups,10 in each group were injected with HCPT lyophilized powder, nano-formulations,5mg·kg-1 of dosage after administration of 15min, blood from inner canthal, the drug concentrations of the liver, liver tumors and blood were determined; divided into 3 groups of the other 33 of physiological sodium chloride based, HCPT injection and the nano-treated,10 in each, administered of dosage of 5mg·kg-1 in the first and fouth day of twice a week, time was 2 weeks. the drug concentrations of the liver, liver tumors and blood were determined from inner canthal of two weeks later.②to record weight changes; observe the growth of implanted tumors and changes of pathological in the state; calculate the rate of tumor inhibition, according to tumor size; test MTT and the mouse tumor cell apoptosis in tumor detection; calculate LD50.Results:①the highest blood concentration of the nano-formulations of HCPT with administrated after 15min was 612.32±21.12ng/ml, the drug concentration of nano-HCPT in the liver and cancer was 11-12 times that of HCPT injection; the drug concentration of HCPT liver cancer were 89.45±16.35 ng/ml and 93.74±18.91 ng/ml after two weeks, the difference between nano-HCPT concentration in liver and liver tumors and blood (2.13±0.51 ng/ml) was statistically significant (P <0.05).②Compared with control group, HCPT injection group and nano-preparation group can inhibit the growth of liver cancer in mice in situ, the inhibition rate of nano-HCPT was higher than the injection group (p<0.05); the inhibition rate was 48.76%. MTT Display:the inhibition rate to the tumor cells and liver cells of nano-HCPT were 82.63% and 27.1%, the apoptosis rate of nano-HCPT group was 49.72±7.51%, according to results of flow cytometry markers.③LD50 determinated was 136.45±18.79 mg/kg.Conclusion:Compared with injection-type HCPT, The nano-HCPT can stabilize the lactone ring structure and increase the organizational affinity and improve the targeting efficacy, which was a new form of improved reliability.