Dissertation > Medicine, health > Pharmacy > Pharmacy

The Experimental Research of Heated Lipiodol-Doxorubicin Pharmaceutics

Author YangLi
Tutor WangZhiMin
School Fourth Military Medical University
Course Medical Imaging and Nuclear Medicine
Keywords Adriamycin (ADM) Ultra-Fluid Lipiodol (UFL) Suspension Emulsion Nanoemulsion Stabilization Biodistribution
Type Master's thesis
Year 2004
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Transcatheter arterial thermo-chemical embolism is a kind of interventional therapy method applied to the treatment of liver rumor in recent years, which has confirmed by experiment and clinical practice. This method has the mixed kill ability of the thermo-therapy, chemotherapy and embolismotherapy to the tumor. Its curative effect has direct relationship with the biodistribution and pharmacokinetics of the pharmaceutics, though it has several different facters. This research concentrates on the heated Lipiodol-Doxorubicin pharmaceutics, which would be the reference for the advanced experimental research and clinical application.Objective: To investigate the significance of the physicochemical properties of three types of Lipiodol-Adriamycin pharmaceutics (Emulsion , Suspension , Nanoemulsion) and the biodistribution of Suspension after heated.Methods: Ultra-fluid lipiodol Adriamycin emulsion (UFI-ADM Emulsion, UAE) and ultra-fluid lipiodol Adriamycin suspension (UFI-ADM Suspension, UAS) was prepared by "pumping technique". Ultra-fluid lipiodol Adriamycin Nanoemulsion (UFI-ADM Nanoemulsion, UANE) was prepared by mechanical and ultrasound emulsifier homogenizer after Tween-80 and Span-80 had added to the UAE.After heated up at different temperature of 25 C , 40C, 50C,60C for two hours, the time of delamination and sediment of the three types of pharmaceutics was counted, the viscosity was measured, the form of the particle was observed by the microscope and electron microscope, the concentration of ADM in liquid of dialysis was measured by ultraviolet spectrophotometic method for the ADM releasing rate and embedding ratio.UAS (4mg/ml) of normal temperature and 60C was infused into liver cancer model of vx2; Investigated by DSA, CT, Ultrasonograph, and observe pathological section dyed with oil red by microscope and confocal microscopy for the biodistribution of UFI in the tissue of the tumor. The concentration of ADM in the tissue of tumor measured by ultraviolet spectrophotometic method for the ratio of concentration of ADM. (the ratio of measured concentration to the total priming volume).Results: After heated up the delamination and sediment of UAS and UAE speeded up. In the sight of the microscope, the heated pharmaceutics had more big particulate/oil-drop. In comparison with the degree of 25 C, both the relative viscosity and the relative viscosity ratio of the two pharmaceutics reduced about two times at the degree of 60C, the releasing rate was lower. Among the groups at the degree of 25C 40C, 50C . each pharmaceutics had nearly the same releasing rate(P >0.05). In the group at the degree of 60 C , the releasing rate of UAS, USE and Adriamycin-Saline solution almost had no difference(p>0.05).The UANE had an appearance of pink, stable, creaming not observed within the observing period; under transmission electron microscopy , UANE showed a global , regular contour with homogenous size and distribution. The particles ranged from 8-26nm in diameter, with 18.3 + 8.0nm as the average diameter. The embedding ratio was 92.6%. The maximum releasing ratio was 93.39%, and the time of semis releasing was 7 hours.After heated up at different temperature of 25C, 40C, 50C,60C for two hours, no creaming was observed within the observing period(7h). With the increasing of temperature, the viscosity of UANE decreased about one time. The drug releasing ratio was decreased: ranged from 25 C to 60 C, the time of semis releasing was delayed, which was 7h, 20h, 72h, >72h; Platform period of concentration was 24h, >72h, >72h, >72h; the ratio of peak concentration to that of 25 C was 1.00, 0.77, 0.53, 0.43. Speed of drug releasing was slower. Result observed by X-ray in the operation indicated that the heated pharmaceutics had a character of easy controlling compared with the normal one. The heated one had little oil drop under the fluid condition. Post-operative DSA indicated that heated one had a high dense in the field of tumor. Power Doppler Ultrasonograph (PD-US) examining after operation ind

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