Study On The Targeted Permeability Of Superparamagnetic PTX Liposome Across Blood-brain Barrier

Background:Malignant astrocytoma is the most common primary brain tumor to the adult and results in serious harm to the health.It is almost unfeasible to be completely resected because of its aggressive nature,the fine structure and the unique role of the brain.Chemothrapy has advantage over operation in this respect but blood-brain barrier,p-gp,et al exclude many chemotherapeutic agents that are sensitive to brain tumor cell lines in vitro assays.Objects:Prepare superparamagnetic paclitaxol liposome(SMPL) and investigate its brain targeting in magnetic field and the meanings of injecting via carotid artery to brain targetingMethods:1.Preparing and characteristics of SMPL:Take paclitaxol(PTX) and Fe₃O₄ as the chemotherapeutic agents to prepare SMPL by reverse-phase evaporation.Its characteristics were studied with transmission electron microscope(TEM),vibrating samples magnetometer,high performance liquid chromatography(HPLC),et al.2.Animal experiment:(1).Male Wistar rats were randomly assigned into three groups:A,B and C group.Rats were injected with agents(2.5ml/kg,the concentration of PTX is 1.0mg/ml)via carotid artery.A group was injected with SMPL suspension and then the head of rat was placed in magnetic field.B group was injected with SMPL suspension and C group with PTX solution.The brain tissues were harvested 1h after injecting and were dyed with Prussian blue staining method.(2).Mail Wistar rats were divided to 3 groups and injected via dorsal penis vein with the same agents(5ml/kg,the concentration of PTX is 1.0mg/ml) that were injected in animal experiment(1).The rat brains of 3 groups were harvested respectively 1h,4h,8h,16h after injecting.The concentration of PTX in rat brain was measured by HPLC test.(3).Male wistar rats were divided into 2 groups,one group was injected with SMPL suspension(5ml/kg) via dorsal penis vein and the other group was injected with SMPL(1ml/Kg) via carotid artery.The head was placed in magnetic field for 1h and then the brain was harvestded.The concentration of PTX in rat brain was measured by HPLC test.Results:1.characteristics of SMPL:The SMPL is globular and 15nm in mean diameter.Magnetization curve of SMPL indicates the character of superparamagnetism.The encapsulation ratio is 99.76%.2.Animal experiment:(1). The density of Prussian blue staining-positive particles in rat brain tissue of A group was obviously higher than that of B group and no Prussian blue staining-positive particle was observed in C group; (2).The PTX concentration in rat brain of A group is higher than that of B group,and PTX concentration of B group is higher than that of C group.(3).The PTX concentration in brain of the rat that was injected via carotid artery(1ml/kg) is obviously higher than that via dorsal penis vein(5ml/kg).Conclusions:1.SMPL is a kind of ideal superparamagnetic nano vector. 2.SMPL is capable of taking Fe304 into brain tissue and even neurocyte nucleus, and the magnetic field promote the activity across BBB.3.SMPL is capable of taking PTX into brain tissue.The magnetic field can significantly increase the PTX concentration in rat brain.4.The way of injecting via carotid artery increased agent concentration in rat brain tissue drasticly than that via vein.