Development Of Tetrandrine Liposome

Tetrandrine, a lipophilic alkaloids, which was extracted from dry root of Stephania tetrandra S. Moore. It had a wide range of pharmacological effects such as anti-inflammatory, analgesic, anti-silicosis, anti-fibrosis, and so on. It was more satisfied drug which was the treatment of acute and the rapid progress of silicosis. Because tetrandrine was difficult to dissolve in water, the shorter half-life, low bioavailability, toxic to cells, clinical application of tetrandrine was limited.Liposomes, as a new drug carrier, had similar biomembrane structure, cell-friendly and organizational compatibility,without inhibition and damage to normal cells and tissue. It could encapsulate the drug with various physical and chemical properties, solve the problem that lipophilic drugs were difficult to insoluble in water, chang distribution of the drugs in the body, delay the release of drugs, So it could reduce the dose and toxicity, improve therapeutic index of drug. This dissertation developed tetrandrine liposomes, extended the tetrandrine liposome stagnation in the blood, increased bioavailability.Firstly HPLC was established to determine drug content of tetrandrine liposomes, the method was accurate and reliable. The encapsulation efficiency was investigated by dialysis.A variety of liposomes preparation methods was investigated, and then film dispersion-sonication method was found to be best with higher encapsulation efficiency and better stability. After screening by orthogonal experimental design, the optimized formula was Cholesterol:Phospholipid was1:10 (W/W), Drugs:Phospholipid is1:12 (W/W), Tween-80:Phospholipidis1:5 (W/W), hydration medium was pH 6.5 PBS. Optimum preparation process : water bath temperature was 50℃, hydration temperature was 30℃, ultrasound 13 min, ultrasonic power was 120W.This dissertation investigated the Pharmacy nature of the liposome. Through TEM, tetrandrine liposomes were spherical vesicles, the size was 230 nm, The surface Zeta potential was -7.7 mV, liposome encapsulation efficiency was 79.7%. In vitro hemolytic characteristic of tetrandrine liposomes was investigated by naked eyes and hemolysis test. Tetrandrine liposomes in vitro did not have hemolysis.The levels of tetrandrine liposomes in rat plasma determinated by HPLC; plasma concentration of tetrandrine liquores and tetrandrine liposomes in rats was measured by HPLC. According to compartment-model fitting results, tetrandrine liquors were fitted for two compartment-model, T1/2αwas 3.18min, T1/2βwas 371.69min; Tetrandrine liposomes were also fitted for two compartment-model , T1/2αwas 3.20min, T1/2βwas 755.90min. Which showed tetrandrine liposomes extended stagnation in rat blood.