Preparation Of The Delayed Drug Release Nanoparticles Of Kurarinone And Their Pharmacokinetics And Targeting Research In Rats

Kurarinone is also known as oxymatrine. Basic pharmacological and clinical studies have shown that it has anti-cancer, anti-virus, anti-parasitic, anti-inflammatory, anti-arrhythmic and significantly increased the role of leukocyte and has broad prospects of development. In recent years, its role in the treatment of viral hepatitis is also obvious. However, the half-life of the drug after intramuscular injection is very short, the selectivity of tissue distribution is poor, and it has certain side effects. By changing its form to improve the bioavailability of drugs and reduce drug side effects is a more effective way.Nano-drug delivery systems ,targeted at implementation and release drug delivery, as well as insoluble drugs improve bioavailability, reduce side effects of drugs, etc. have good application prospects. PLGA,because of its excellen biocompatibility and biodegradability,has been widely used as nano-ball.Carrier material, as the carrier of its NS overcome nano emulsions, nano-liposomes and other drug easily leak disadvantage, to become one of the research at home and abroad for a new type of targeted drug delivery carrier. This paper consists of three parts:Part one: Kurarinone targeted nanoparticles release Preparation of the delayed drug release nanoparticles of kurarinone and to examine the impact of factorsPLGA in this study is as a carrier, Pluronic F68 is as emulsifiers. KU-PLGA-NS was made by precipitation method , observed by TEM,and drug contents were measured by HPLC.The average rate for the encapsulation is 79.5%.The average amount of the drug is 1.75% .The average size is 190.5nm. KU-PLGA-NS essentially meet the design requirements. the preparation is expected to become a new drug targeting vector system.Part two: The establishment of analytical method of KU in biological matrixA reversed-phase high-performance liquid chromatographic(RP-HPLC) method has been developed for the determination of KU in rat plasma, bile, urine, feces and tissue homogenates. The sample pretreatment included deproteinization for plasma samples and a liquid-liquid extraction for bile, urine, feces and tissue homogenates. Separation was obtained on a Kromasil C₁₈ (150×4.6mm, 5um),using an excitation wavelength of 229nm.The isocratic mobile phase consisted of methanol-0.01mol/l potassium dihydrogen phosphate buffer(65:35,v/v) was run at a flow rate of 1.0 ml/min for different biological matrix. Column temperature was 30℃. The chromatographic system used provided good separation of the compound without interfering peaks from endogenous substance. The calibration curves were linear in each sample range with correlation coefficient above 0.99.The precision of intra-day and inter-day were evaluated by analysis of variance with the result of 0.7².3% and 0.7⁶.4%, respectively. The method has been successfully used to support the pharmacokinetics study of KU.Part three: The pharmacokinetics, tissue distribution and liver targeting authentication study of KU-PLGA-NS in rats.A single dose in rats by intraperitoneal injection of large, medium and small three-dose Oxymatrine nanoparticles and the dose of drug oxymatrine, in accordance with rats when the plasma concentration by the process, to estimate the corresponding pharmacokinetic parameters. The metabolism of KU following oral administration accords with the linear relation, and its blood plasma Cot curve consists with the first order kinetics of one compartment model.T_1/2Ke (min): 90.71±2.34,91.69±1.94,92.45±2.49;AUC_0-tn(mg/L.min):217.36±78.87,785.17±170.21,996.24±165.43;C_max(mg/L): 11.82±2.29,28.48±5.40,40.21±5.13;T_max(min):10.00±0.82,10.10±0.64,10.20±1.21;To 36 rats were randomly divided into 2 major groups, each group further divided 3 large groups, each group 6, 2 channel tube big group of matrine administration and preparation of raw materials have been targeting the release of nano Kurarinone ball. SD Rats were killed by exsanguination after a certain period of time , quickly remove the heart, liver, spleen, lung, kidney, stomach, intestine, muscle, skin, thymus, brain, uterus, testis, bone marrow and fat. Deal with liquid-liquid extraction of various biological samples. Again in accordance with the conditions of 2, different samples measured the concentration of kurarinone. Kurarinone control of raw materials and drugs, nanoparticles Kurarinone liver tissue at the peak concentration of drug increased. This shows that nanoparticles Kurarinone liver tissue at the drug concentration and distribution of a higher percentage, showing a clear effect of liver targeting. 120 rats were divided into two groups by the method of equlilbrated and equally divided between male and female, by intraperitoneal injection of KU-PLGA-NS and raw materials, observed targeting situation, was obvious effect of liver targeting, optimization and reasonable process.