Study On The Targeting Chemotherapy Using Magnetic Paclitaxel-Suspension Administered Subcutaneously Against Lymph Node Metastasis

Objectives: (1) To prepare magnetic paclitaxel-suspension. (2) To investigate the new dosage form of paclitaxel about its magnetic targeting and stagnation in regional lymph nodes. (3) To evaluate the efficacy of this kind of chemotherapy against lymphatic metastasis in mice.Methods: (1) Microparticle of activated carbon and magnetic powder, polyvinylpyrrolidone were mixed with paclitaxel in alcohol solution by ultrasonic. (2) The magnetic paclitaxel-suspension was injected into tubing, at proper site where a permanent magnetic field was applied. The paclitaxel concentrations of these samples being taken from near and far away from the magnetic fields were detected by high performance liquid chromatography respectively. (3) The H22 ascites tumor cells were inoculated subcutaneously into the foot-pad of the left hind paw of mice to set up the animal models of lymphatic metastasis. (4) 120 mice were divided into two groups. The permanent magnetic blocks were fixed on the surface of left inguinal lymph nodes in one of the two groups. The concentrations of paclitaxel in lymph nodes being gained at a series of time after subcutaneous injection of the magnetic paclitaxel suspension in left thigh were assayed. (5) 100 mice were allocated into five groups randomly, group A: no treatment; group B: magnetic fields use only; group C: magnetic carrier without paclitaxel; group D: magnetic paclitaxel suspension only; group E: magnetic paclitaxel suspension with magnetic fields. All mice were sacrificed on day 12 after various interventions, then half of the left inguinal lymph nodes were weighed and fixed in 10% formalin for histologic examination,the rest were minced in aseptic conditions and transferred intraperitoneally to 50 normal recipient mice for the estimation of the numbers of viable H22 tumor cells in lymph nodes. Results: (1) The magnetic paclitaxel-suspension was black and well-distributed, pH=6.8±0.1, the size of particles was about 188nm, the average dosage of paclitaxel in this new dosage form was 0.994g/L. (2) The concentrations of paclitaxel in tubing near the magnetic fields were significantly higher than that far from magnetic fields(1.212±0.049g/L vs. 0.785±0.085g/L, P<0.01); the mean peak concentration of paclitaxel in lymph nodes being covered with magnetic fields was higher than that of control group (4.530±0.270μg/g vs. 3.044±0.411μg/g, P<0.01), and the time which paclitaxel could be detected was longer than that of control group(254h vs. 206h). (3) Compared with the other groups, there was a significant weight loss in left inguinal lymph nodes being covered with magnetic fields following subcutaneous injections of magnetic paclitaxel-suspension (P<0.01 or P<0.05), and the general survival rate of tumor recipients was significantly higher. Conclusion: With the characteristics of lymph targeting and being detained lastingly in regional lymph nodes by magnetic field, the magnetic paclitaxel-suspension injected subcutaneously is effective for the treatment of lymph node metastasis in mice.