| TAE (transcatheter arterial embolization) is a technology that releases the substance which cause lumen temporary or permanent blocking through the catheter into the vascular lesions or lesions of the artery occlusion, the use of anti-cancer drugs or drug microsphere embolization can play the role of chemoembolization.According to the characteristics of Targeted microspheres via artery embolization, its pharmacokinetic study is peculiar and difficult. Especially in the case of the microspheres with drug after artery embolization, the drug concentration detection of the local target tissue has been a problem. The main reason is that the sampling method of targeted tissue can not rule out the effect of intravascular drug residues.To clarify drug concentration and absorption of loacl target tissue after arterial embolization, in this study, we dissociated the femoral artery, took femoral artery blood vessels, filled in a certain amount of RFP-KMG, embed the sac bag immediately. According to the schedule, biological membrane sac bag was taken out, detect the remaining dose of sac bag, the concentration gradient of the liver tissue, peripheral blood drug concentration detected, release characteristics of drug-loaded microspheres embolization in liver tissue was studied, in order to establish a new method to detect drug concentration of drug microspheres artery embolization.The RFP-KMG was provided by the company, in vitro release test conditions (0.4%bovine serum albumin in PBS buffer;37℃;80r·min-1), it was up to release platform about3days, and about3to21days sample release was basically stable. But there was a sudden increase about28days. Within28days of sampling, the microspheres sample of dialysis bag has completely dissolved. It became concentrated liquid sample, and sample release showed a burst release at28days.This project was to establish a method of detecting local tissue drug concentration in animal experiments which would set up microsphere embolization delivery system with drugs, product the microspheres with drug embolic agents artery pouch, embed it in the liver, and accurately examining its local tissue drug concentrations and release characteristics,1Liver embedding experiment30male white New Zealand rabbits were divided into five different groups randomly, with six rabbits at a group,(the RFP-KMG experimental group n=5, the blank control group n=1). The first step was to make a biological membrane sac bag. Remove the hair of inner thighs after anesthesia, dissociate the femoral artery, take about3cm femoral artery blood vessels, fill in a certain amount of RFP-KMG or sodium alginate microspheres embolic agents, ligate the blood vessels in both sides, and then the sac bag was immerged in normal saline. The second step was to embed the sac bag. Remove the hair of abdmen-thorax after anesthesia, and incise the midsection with a transverse incision, then expose the liver and embed the sac bag immediately, stanch the wound with gelatin sponge and then feed them normally. Blood samples were obtained from ear vein according to the schedule, and biological membrane sac bag was taken out with embedding point as the center.2Liquid phase of biological sampleHPLC method was used for detecting the rifampicin of plasma samples and tissue samples. The chromatographic column was an Diamonsil ODS-2(4.6X250mm,5μm) with a mixture solution of methanol-acetonitrile-0.075mol-L’1potassium dihydrogen phosphate solution-1.0mol·L-1citric acid solution (30:32:36:4) as the mobile phase, at a flow rate of1.0ml·min-1. The column temperature was35℃. The detection wavelength was254nm, and the sample size was6mL. Methodological study was applied to detect, and the RSD of rifampicin content which was less than5%precision in reproducibility, stability and recovery test, and it was in line with the requirement of experiment. The results showed that chromatogram of rifampicin had a good separation and sensibility. The number of theoretical plates of rifampicin in sampales were more than5000, and the retention time was15.52min, it was well-separated with other chromatograms, whose resolutions were bigger than3, and it can be used in pharmacokinetic study3Metabolism Research of RFP-KMGWere detected the rifampicin concentration of plasma samples, tissue samples, the sac bag with rifampicin with HPLC methods. The data was analyzed with PKSolver2.0pharmacokinetics software,The best weight and compartment model were selected according to the least AIC values and the largest correlation coefficient was obtained from real concentration.The results showed that compartment modle was fitted well with open two-compartment model after being embeded the sac bag with rifampicin. With the embedding point as the center, rifampicin concentration was gradually increasing from proximal end to distal end of liver.1day after being embeded, the percentage of metabolic residual is (74.59±1.48)%,3days after being embeded, the percentage of metabolic residual is (52.56±1.24)%,1weeks after embedding, the percentage of metabolic residual is (33.11±1.95)%,2weeks after being embeded, the percentage of metabolic residual is (19.48±1.87)%,1months after being embeded, the percentage of metabolic residual is (1.34±0.6)%. |
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