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An Exper Imental Study On Thermal Targeting Property Of Natural Phospholipid Liposomes Encapsulated Antitumor Drugs Combined With Hyperthermia

Posted on:2001-09-11Degree:MasterType:Thesis
Country:ChinaCandidate:F ZhaoFull Text:PDF
GTID:2144360002951233Subject:Surgery (general surgery Professional)
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on thermal targeting property of natural phospbolipid liposomes encapsulated antitutmor drugs combined with. hyperlhermia ABSTRACT In recent years,the method of antitumor is hot point. The therapeutic efficacy of all chemotherapy means treating tumor is not significantly greater. Single-modality therapy to tumors not oniy can~t focus on antitumor drugs to tumor invaded zones but also increase side effect. So we must reseach multimodality themotherapy in order to enhance antitumor efI~ct and survival rate. The aim of this study was to determine whether natuml lipid can be made thermosensitive liposome for instead of synthetic lipid and involving a combination this liposome with local hypertherniia would result in enhancement of therapeutic efficacy for tumors. At first we research the preparation of thermosensitive liposome loading drug derived natural lipid. The second we investigated that the combination of it with local hyperthermia at the tumor site whether could be useful in enhancing drug delivery to tumors and improving its therapeutic eflicacy in treatment of ascites and solid tumors. lThe study of preparation of thermosensitive liposomea by made of natural lipid and thermal targeting delivery in combination with local hyperthemia. Herein we use natural lipid ,viz:soya phosphatidy 1 choUne,cholesterol,organic solvent to prepare thermosensitive small unilamellar liposomes with different proportion and temperature .In order to avoid reticuloendothelial system (RES) uptake and prolong systemic circulation of antitumor drugs encapsulated thermosensitive liposomes. Ploy ethylene glycol (PEG) was incorporated as membrane modifiers into lipid bilayers composed of soya lipid and cholesterol. Our results suggest that heat-sensitive liposome made of natural lipid by proper proportion among compounds and fixed method also have phase transition temperature (42C)as same as synthetic lipid in -4- vitro. Thermosentive liposome entrapped I3~I have been tried for targeting drugs to heat invaded zones. It showed lower RES levels than the control general liposomes.This type of thermosensitive liposome should be more useful in hyperthermia-mediated targeted tumor drug delivery systems than the thermosensitive liposomes without the modifiers (PEG) to avoid RES uptake. 2 Research of effects of tumor-bearing Nude Mice being intravenously administered with therinosensitive Iiposomes loading antitumor drugs. We applied the animal model of nude mice with peritoneal and endermic plant of human colon cancer (LoVo) cell. The experiment consisted of four groups: 1 received free drugs.and 42 degreesC local heating for 30mm ; 2 received heating for 30mm ; 3 received Iiposomes containing drugs and heating for 30mm ; 4 control groups .Conclusion: A significant reduction in tumor volume and an increase in survival time was observed in tumor- bearing mice treated with a combination of hyperthermia and thermosensitive liposome encapsulated antitumor drugs compareing with animals treated with an equivalent dose of free drugs with or without hyperthemia . we suggest that the use of thermosensitive liposomes and hyperthermia not only contributes to the tumor killing as direct thermal killing does but also helps to increase the concentration of chemotherapeutic drugs into th...
Keywords/Search Tags:Natural soya phosphatidylcholine, Cholesterol, Thermosnsitive, liposome Phase, transition temperature, Long circulation liposonies, Tumor-bearing nude, mice Hyperthermia and chemotherapeutic, tumor Antitumor effect
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