Preparation Of Paclitaxel Magnetic Nanoparticle Liposome And Its Tissue Distribution In Mice

Malignant tumor is one of the most urgent problems around the world in both life scienceand medical science area. Facing the increasing death rate, researchers have being makinggreat efforts to develop one new curing method or dosage forms which may effectivelyovercome the limitation of existing treatment. There was widespread sentiment in medicalprofession that early operation and the later chemotherapy treatment will significantlyimprove the outcome of this kind of disease. The appearance of targeted therapy provides amore feasible and effective way for chemotherapy, and promotes the emergence anddevelopment of new dosage forms. Paclitaxel was found in this case. It is a new and effectiveanti-cancer liposoluble drug, its special anti-cancer mechanism makes it effective to ovariancancer, lung cancer, breast carcinoma and so on, but the clinical toxicity and lowbioavailability limits its further application because of the poor water solubility. Liposome isa drug carrier with both hydrophilic and lipophilic properties which has been successfullyapplied as drug delivery systems. So this issue aims at preparing a safe and efficient paclitaxelliposome formulation, putting in the magnetic powder and resolving the clinical applicationproblem of paclitaxel in the presence of an applied magnetic field. The main research andresults are as following:Preparation of paclitaxel magnetic nanoparticle liposome: the ultrasound membranedisintegration method was used to prepare the paclitaxel magnetic nanoparticle liposome.Through the orthogonal design, the method was optimized with encapsulation ratio anddistribution conditions as the most technique parameters. The results indicated that the idealcombination of preparation and formulation were as follows:lecithin:cholesterol(4:1),paclitaxel:(lecithin+cholesterol)(1:30), the time of ultrasound(30min), magnetic powder:paclitaxel (1:1), tween-80:paclitaxel(4:1), polyethylene-1000:paclitaxel(6:1). The averageencapsulation rate of the optimized liposome was (84.4±1.7)%,the average particle sizewas(150±20)nm, it shows great delayed release effect in 48h. The results showed paclitaxelmagnetic nanoparticle liposome has high encapsulation ratio, even distribution, and it also hasdelayed release effect , accord with requirements of targeted drug delivery system.The inhibition effects on human cancer cells growth in vitro were investigated: weprepared blank liposome, magnetic liposome, paclitaxel solution, paclitaxel liposome andpaclitaxel magnetic liposome, chose lung cancer, breast cancer and pancreatic carcinoma cells,and then we use MTT Cell Proliferation Assay to investigate the suppression effection. Theresults show that paclitaxel magnetic liposome has better inhibitory effect compared to other group, and they also show sustained-release effect to a certain extent in 48h .Distribution of paclitaxel magnetic liposome in both blood plasma and tissues: first, weget the LD50 is 61.64 mg/kg by the acute toxic experiment. Then we choose paclitaxelliposome as control and paclitaxel magnetic liposomes to do our research, and give thepaclitaxel magnetic liposomes group a magnetic field with the magnetic intensity 0.5T nearthe lung of the mice. The contents of the two groups in various main tissues (heart, liver,spleen, lung, kidney) and blood plasma of mice are determined at the points of 15min, 30min,1h, 3h, 6h, and 12h after injection emulsion of paclitaxel liposome and paclitaxel magneticliposome at mice tails. The results showed that the paclitaxel magnetic liposomes group wasdetected higher drug concentration in lungs compared to the control(even 4 times then thepaclitaxel magnetic liposomes group), and can not recede in a few hours, which shows goodmagnetic targeting role in the distribution, the drug distribution is also different in othertissues compared to the control.The paclitaxel magnetic liposome we prepared has good characters , basicly satisfied therequirement of target drug delivery system. Our study indicated that paclitaxel magneticnanoparticle liposomes are expected to achieve anticancer effects in further clinical drug trial.Targeting therapy could be a novel approach to the cancer treatment.