ABSTRACT
OBJECTIVE To study the pharmacokinetic behavior of novel lung-targeted Docetaxel liposome （DTX-LP） in in- situ lung cancer model rabbit. METHODS The content of DTX in rabbit plasma was determined by UPLC-MS/MS， and methodology investigation was conducted. in-situ lung cancer model rabbit was made by the ultra-minimal invasive percutaneous puncture inoculation method. Model rabbits were randomly divided into Docetaxel injection （DTX-IN） group and DTX-LP group. The rabbits were given relevant medicine via ear vein at a dose of 1.0 mg/kg （calculated by DTX）； blood was taken at 5， 15， 30， 60， 90， 120， 240 and 480 minutes to measure the concentration of DTX in plasma. DAS 3.3 software was adopted for fitting and analysis， and to calculate pharmacokinetic parameters. RESULTS UPLC-MS/MS method used in this study was accurate and precise， which met the requirements of biological sample analysis. Compared with DTX-IN group， drug concentration-time curve of DTX-LP was smoother， the blood concentration at each time point was lower， and cmax， t1/2， AUC0→480 min and AUC0→∞ were significantly decreased （P＜0.05）. CONCLUSIONS The drug exposure of DTX-LP in plasma is significantly reduced than DTX- IN， indicating it can be rapidly distributed from systemic circulation to liver target organs.
ABSTRACT
The purpose of the present work is to establish an ultra-minimal invasive percutaneous puncture inoculation method for a VX2 orthotopic lung cancer rabbit model with fewer technical difficulties, lower mortality of rabbits, a higher success rate and a shorter operation time, to evaluate the growth, metastasis and apoptosis of tumor by CT scans, necropsy, histological examination, flow cytometry and immunohistochemistry. The average inoculation time was 10–15 min per rabbit. The tumor-bearing rate was 100%. More than 90% of the tumor-bearing rabbits showed local solitary tumor with 2–10 mm diameters after two weeks post-inoculation, and the rate of chest seeding was only 8.3% (2/24). The tumors diameters increased to 4–16 mm, and irregularly short thorns were observed 3 weeks after inoculation. Five weeks post-inoculation, the liquefaction necrosis and a cavity developed, and the size of tumor grew further. Before natural death, the CT images showed that the tumors spread to the chest. The flow cytometry and immunohistochemistry indicated that there was less apoptosis in VX2 orthotopic lung cancer rabbit model compared to chemotherapy drug treatment group. Minimal invasive percutaneous puncture inoculation is an easy, fast and accurate method to establish the VX2 orthotopic lung cancer rabbit model, an ideal in situ tumor model similar to human malignant tumor growth.
Subject(s)
Humans , Rabbits , Apoptosis , Drug Therapy , Flow Cytometry , Immunohistochemistry , Lung Neoplasms , Lung , Methods , Mortality , Necrosis , Neoplasm Metastasis , Punctures , Thorax , Tomography, X-Ray ComputedABSTRACT
OBJECTIVE:To establish a method for the content determination of baicalin in Yangyin mixture. METHODS:HPLC was performed on the column of SunFire C18 with mobile phase of methnol-water-phosphoric acid(43∶57∶0.2,V/V/V)at a flow rate of 1.0 ml/min,the detection wavelength was 280 nm, column temperature was 30 ℃,and the volume injection was 10 μl. RESULTS:The linear range of baicalin was 0.055 75-1.115 μg(r=0.999 9);RSDs of precision,stability and reproducibility test were lower than 2%;recovery was 95.39%-98.44%(RSD=1.19%,n=6). CONCLUSIONS:The method is simple,rapid and accurate,and suitable for the content determination of baicalin in Yangyin mixture.
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Objective To explore the influence of fluoxertin on level of IL-2 ,IL-6 and TNF-α in brain tissue and serum of rats with post-stroke depression(PSD) .Methods 60 rats were divided into sham operation group ,depression group ,stroke group ,PSD group and fluoxertin group ,12 cases in each group .ELISA was used to detect the level of IL-2 ,IL-6 and TNF-αin brain tissue and serum .Results The level of IL-2 ,IL-6 and TNF-αin depression group ,stroke group and PSD group were significantly increased and higher than that in sham operation group and fluoxertin group(P0 .05) .Conclusion Fluoxertin could significantly decrease the level of IL-2 ,IL-6 and TNF-αand play an important role in therapy of PSD .
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Objective:To prepare EC impermeable capsule bodies for pulsatile drug delivery system and evaluate the effects of different species dichlormethane mixed solvent and concentration of EC(ethyl cellulose) solution on EC capsule bodies. Methods:The EC impermeable capsule body was prepared by filling method with the EC solution composed of different dichlormethane mixed solvent. The influencing factors on the forming of the EC capsule and the inosculation between the EC capsule and corrosion tablet were investigated by dissolution tester,hardness tester,multifunction pachometer and Sliding caliper. Results:The EC capsule body that was prepared by 11.5%(w/v) 45cp EC solution using the mixedsolvent composed of dichlormethane/ethanol absolute/ethyl acetate(4/0.8/0.2) inosculated well with the corrosion tablet and met the requirements of the pulsatile drug delivery system. Conclusions:The solvent and concentration of the EC solution have great impact on the forming and characterisitcs of the capsule bodies,by optimazing the preparing methods, requirements of the oral pulsatile drug delivery system can be met.
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Objective To prepare thermosensitive in situ gel of ibuprofen ( IBU) inclusion complex with poloxamer and evaluate its release behavior in vitro and in vivo. Methods The IBU inclusion complexes were prepared by lyopyilization. The poloxamer 407 and 188 were added as a base for the preparation of gel. The release of inclusion complex gel was evaluated by membraneless models. The pharmacokinetics was evaluated after intramuscular injecting IBU solution or IBU inclusion complex gel to New Zealand white rabbits. The drug concentrations in the plasma were measured by HPLC. Results The loading amount of IBU was 10. 24% . The corrosion of gel and the release of IBU correspond to zero-order kinetics. Compared with IBU solution,the tmax and t1/2 were prolonged and Cmax was degraded while AUC was enhanced obviously. Conclusion The IBU inclusion complex gel is used as a good injection with sustained-release which can improve the analgesia and an- ti-inflammatory effect of ibuprofen. And our study builds up the foundation for the use of water-insoluble drug in thermosensitive in situ gel.