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Preparation Of Doxorubicin Sustained Release Microspheres And Effects On Breast Cancer

Posted on:2013-07-09Degree:MasterType:Thesis
Country:ChinaCandidate:Y LiFull Text:PDF
GTID:2234330395986195Subject:Microbial and Biochemical Pharmacy
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Breast cancer is a common disease that seriously threatens women’s health. The chemotherapy is one of most effective common methods in Cancer therapy. But generally the chemotherapeutants-have no specific selectivity between the normal cells and the tumor cells. The intratumoral drug concentration remains at a low level by the systemic administration, and side effects are usually serious. This limits the high dosage administration and clinical efficacy of the anticancer chemotherapeutants. The chemotherapeutants appear to inhibit tumor effectively in vitro, but not effective in vivo. The reasons for this are possibly due to some influential factors.like the form of prepared drugs, the administration methods and the internal environment. The therapeutic efficacy could be improved by changing the form of prepared drugs, the administration methods and prevention of the internal interference. So the microspheres, which arc characterized by controlled release, sustained release and long-persistent effect, is regarded. The intratumoral injection of microspheres could maintain a high drug concentration in the tumor and continuously act on the tumor ceils, which could improve the efficacy and reduce the side effects.The objective of there research is to prepare Doxorubicin-loaded alginate chitosan-gelatin microspheres, evaluate its physicochemical properties in vitro. High potentiometric dispersion technique was used to prepare DOX-MP microspheres. Its morphology and size was observed vio electronic microscopy, and its drug loading, encapsulation efficiency and drug-release rate were measured. The inhibiting rate of DOX-MP was evaluated by MTT in vitro. The active of the cell was evaluated by AO. Distribution of cell cycle and rate of apoptosis were determined by flow cytometry. Efficiency and drug-release rate were measured.Mice models with transplanted subcutaneous breast cancer were build up. Drugs were intratumorally injected into groups of mice, The tumors were weighted and the tumor inhibiting rates of the test groups were calculated. Also they were sliced up and dyed with hematoxylin and esin, and examined generally pathologically.The Doxorubicin microspheres, Its shape was round and smooth, its size was uniform and its diameter was about113-215μm. Its drug loading rate Was6.42%and encapsulation efficiency66.78%. And cumulated release efficiency of DOX was92.59%after7days. The DOX-MP tumor inhibiting rates was higher than DOX. The DOX-MP and DOX tumor inhibiting rates were63.79%and48.28%in vitro. The DOX-MP and DOX tumor inhibiting rates were60.92%and46.40%in vivo.A new kind of valid sustained-release drug was prepared. It proxided a theoretical basis for chemotherapy drug design of breast cancer.
Keywords/Search Tags:Doxorubicin, sustained release, microsphere, high voltageelectrostatic method
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