Preliminary Research Of Paclitaxel In Situ Gel Formulations And Its Pharmacokinetic Properties

Objective:To evaluate the three PTX in situ gel formulation's phase transition and in vitro release behavior,choose one gel preparations to study the pharmacokinetic behavior and tissue distribution in mice.Methods:?The three PTX in situ gel formulation's phase transition and its release behavior in vitro:The gel material PECT joint in different ways to combine with PTX through physical and chemical method to get different types of PTX gel preparation,According to the characteristics of these formulations,using different methods to detect them,with vial flip and rheological method to study the three phase transition behavior of preparations and evaluate their release in vitro,so it can determine whether they can be used as injecting drug;?Determination of PTX in mice plasma by reverse phase high performance liquid chromatography:Diamonsil-C18(250mmx 4.6mm,5?m)was packed in the analytical column and the mobile phase was comp-osed of acetonitrile and water(52:48).The flow rate wasI.OmL·min-1and the detection wavelength was 227nm.The mice plasma samples were extracted with tert-butyl methyl ether and norethindrone used as the internal standard;?pharmacokinetics and tissue distribution of gel vs.PTX injection in tumor-bearing mice in vivo:When the Balb/c mice tumor volume grow to 1.5-2.0cm3 after the tumor inoculation,we were randomized them into 4 groups:Intraperitoneal injection of PTX injection group,intratumoral injection of PTX injection group,intratumoral injection of PECT/PTX injection group and control group.Three experimental groups are administered a single dose of 40mg·kg-1,collecting blood samples from 5 animals in each set of time points.When blood samples taken,take out the heart,spleen,liver,lung and kidney after the mices died.The plasma and tissue concentrations were determined by HPLC method after the appropriate disposal.The pharmacokinetic parameters were calculat-ed based on the concentration-time curve and analyzed by WinNonlin5.3 software.Results:?The three PTX in situ gel formulation's nature detection show that PECT/PTX NPs really belongs to the nano-preparation and PECT-PTX formulation's material PECT is bonded through a chemical bond to connect with PTX;?The calibration curves were linear in the range of 0.1?300.O?g mL·U-1 for PTX,regression equation:Y=0.083X+0.3894(R2=0.9993).The accuracy were ranged from 85%to 115%,the RSD value of stability were all less than 12%and the extraction recoveries of PTX were more than 90.0%from mice plasma.?The PECT/PTX intratumoral injection group's main pharmacokinetic parameters were respectively as follows:T1/2:473.81±195.13(h),Vd:0.315±0.023(L),AUC0-?:1543.59±486.15(mg/L*h),CL:0.027±0.010(L/h/kg),MRT0-?:673.02±50.29(h).Conclusions:?Phase transition behavior and three formulations release in vitro indicate that they can be made of injection for local peritumoral injection and they all have the ability to release the drug slowly in vitro;?The method is simple,sensitive and accurate,these finding can provide reference during pharmacokinetics investigations for the other preparations of PTX.?Compared with the other two groups,the PECT/PTX intratumoral injection group is statistically significant differences in pharmacokinetic parameters and it has the ability to release the drug slowly in vivo.