Study On Hydroxycamptothecin-hspc Liposome Injection

Hydroxycampothecin(HCPT) is a potent antitumor drug, isolated from Nyssaceae in China, it is the one of the DNA topoisomerase I inhibitors. It shows high antitumor activity in vitro and in vivo. It has excellence such as antitumor, low toxicity, broad-spectum anticancer, and it has no acrossing resistance with other antitumor drug. HCPT has been used to cure liver carcinoma, urinary bladder carcinoma, and colorectal cancer, etc. It also has excellence such as being exreted from choler, less effect to urinary system,no effect to kidney, Structure-activity studies have shown that successful inhibition of DNA topoisomerase I by HCPT requires an intact lactose E-ring. In clinical, the sodium injection with lactose E-ring open has low therapy effect, also has serious side-effect, so the research is to find advanced dosage and clinical uses. Liposomes have been used to be a new kind of carrier, they can improve the stability of the drug and carry the drug to the targeting place.In this passage, the liposomes were prepared by HCPT and different supplementary metials, which improve the stability of HCPT and increase its bioavailability. Then, the freeze-dry liposomes were produced by adding lyoprotectetants, which improve the stability of storage.Firstly, Hydrogenated Soy Phosphatidylcholine(HSPC) as carrier, HCPT liposmes were produced by flim-supersonic dispersion method after carrier choice and technique filter. According to the encapsulation efficiency, various factors were studied. The main variables were HCPT/HSPC ratio, F68 concentration, PBS concentration. Eventually employ the L9(34)orthogonal table. The optimized prescription of the HCPT liposomes was: HCPT:HSPC=1:10, F68 concentration 0.8%,PBS concentration 0.05mol/L.Based on the optimized prescription, the protective function of different kinds of cryoprotectants and different quantities of them were examined by the standards of appearance, redispersity and encapsulation efficiency.Then the formation of the inclusion was proved by Differential Scanning Calorimeters, IR, X-ray diffractometry and solubility before and after being liposomes.According to the related request of the appendices of Chinese pharmacopoeia (2005 edition,Ⅱpart), we perfomed the quality analysis to HCPT-HSPC liposome injection including their characters, identification, inspection, quantification,etc. We use HPLC method to perform quantification, which was able to determie the content of methodology and precisely after the groupig chromatography condition and studying of methpdplogy. Then, we established the quality standard of HCPT-HSPC liposome injection. According to this quality standard, we performed quality analysis to laboratory preparations.We investigated the stablity of the three block medium amplified preparation, including stressing testing (illumination, high temperature and high moisture), accelerated testing, long-testing. The results of stressing showed the HCPT-HSPC liposomes are unstable under high temperature and high moisture.