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Suoqin Tang

Suoqin Tang

PLA General Hospital,China

Title: Study on pharmacokinetics of siRNA-survivin nano-liposomes

Biography

Biography: Suoqin Tang

Abstract

Background: Our previous studies revealed that survivin siRNA nano particles are capable of inhibiting liver cancer, colon cancer and cervical cancer cell growth both in vitro and in vivo, yet pharmacokinetic parameters are largely unknown.

Objective: To investigate the pharmacokinetics of nano-liposomal survivin siRNA (CL01-si-survivin) and provide important basis for its biosafety evaluation.

Methods: Male BALB/c mice (aged 8 weeks) were randomly divided into 3 groups(n=8 for each group). Different doses of CL01-si-survivin were injected via the caudal vein in group A (1mg/kg), group B (3 mg/kg) and group C (6mg/kg). Blood samples (0.1ml each) were collected through eye socket vein after injection at the following time points: 0.083(5 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 7, 24, 30 and 48 hours (7 blood collections for each mouse). Real-time PCR was performed to detect the plasma concentration of CL01-si-survivin based on the standard curve, which was made via the following protocol: prepare survivin siRNA solution at the concentrations of 2.0E+07、2.0E+06、2.0E+05、2.0E+04、2.0E+03 pg/ml respectively, collect 10μl of each and another 10μl plasma from healthy male BALB/c mouse and put them together to 190 μL 0.25% Triton X-100 in PBS (TPS)（95℃ water bath），making the final concentrations of survivin siRNA as 1.0E+06、1.0E+05、1.0E+04、1.0E+03、1.0E+02 pg/mL, then run RT-PCR, taking the logarithm of the plasma survivin siRNA concentration as the independent variable, the average Ct value of each concentration level was the dependent variable, the linear regression, the regression equation and correlation coefficient of the standard curve were obtained, and the standard curve was drawn.
Results: The peak plasma concentrations in each group, reached at 15 minutes after injections, were 1042538.00, 6837099.54 and 14631333.15 pg/ml, respectively. The plasma concentration decreased significantly after 24 hours. The pharmacokinetic parameters were analyzed (table 1). The half- life of CL01-si-survivin in each group was 3.60, 2.64, 2.80 hours, respectively. The AUC (area under the curve) values were 952190.88, 6800687.79, 13803680.96 hr*pg/ml and the total drug clearance were 1050.12, 441.13, 434.67 ml/h/kg. Mean residence time (MRT) were 1.70, 1.97 and 2.10 hours respectively. 
Conclusions:The RT-PCR method was successfully applied to pharmacokinetic study of CL01-si-survivin in vivo; The half- life t1/2 at three dosages were closed to 2-4h; Tmax was similar at 15minutes; Cmax and AUC were positively correlated to dosage between 1-6mg/kg; the MRT was close to 1-3 hours.