聚乙二醇-聚己內酯-聚乙二醇團聯共聚物搭載阿黴素之奈米微胞對於裸鼠皮下移植之人類乳癌腫瘤抑制效果

Inhibition Effect of Doxorubicin-loaded PEG-PCL-PEG on the Human Breast Cancer Using a Xenograft Model of Nude Mice

江建霖(Jian-Lin Jiang)

指導教授 ： 謝明發

中原大學/工學院/醫學工程研究所/碩士(2010年)

https://doi.org/10.6840/cycu201001055

摘要

由本研究合成之生物可分解高分子聚乙二醇-聚己內酯-聚乙二醇 (PEG-PCL-PEG) 團聯共聚物形成的奈米微胞，經過動物體外溶血測試得到濃度 2.0 mg/mL以下的奈米微胞溶液具有良好的血液相容性。以未包覆藥物之微胞於動物體內做 14 天急性毒性測試，注射劑量為 71.43 mg/kg，觀察體重變化並沒有發現老鼠體重持續下降的情況，且老鼠存活率為 100 %。進而觀察老鼠的肝臟與腎臟組織切片，其臟器的組織細胞型態屬於正常的情形。kupffer 細胞與 mesangial 細胞分別為肝臟與腎臟裡的發炎細胞，在組織切片中並沒有明顯增多的現象。在單一劑量腫瘤抑制實驗中，注射 doxorubicin 的老鼠在一週內有延緩腫瘤生長情形，注射微胞包覆 doxorubicin 的老鼠在一週後至兩週內的期間有延緩腫瘤生長的情形，並且能降低doxorubicin對肝臟的傷害。而多重劑量腫瘤抑制實驗中，注射微胞包覆 doxorubicin 的腫瘤比注射 doxorubicin 的腫瘤小約 25 %。再經由生物分佈的結果顯示，微胞包覆 doxorubicin 能夠延長在動物體內的血中濃度，由以上結果顯示，生物可分解高分子 PEG-PCL-PEG 具有良好的生物相容性並能搭載藥物延緩腫瘤生長。

關鍵字

聚乙二醇-聚己內酯-聚乙二醇 ； 微胞 ； 奈米粒子 ； 腫瘤抑制效果

並列摘要

In this study, the biodegradable poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG) for the nano-sized micelles synthesized. The in vitro hemolysis test showed that the micelles which concentrations of 2.0 mg/mL or less had good blood biocompatibility. The in vitro experiment of acute toxicity using empty micelles (placebo) at dosage of 71.43 mg/kg showed no apparent change of body weight in mice, and the survival rate was 100 %. Furthermore, in the tissue slices of liver and kidney, the cell morphology was normal. And there was unobvious increasing of kupffer cells and mesangial cells in the liver and kidney respectively. In the tumor inhibition experiment, the mice injected with free doxorubicin (DOX) exhibited the delayed tumor growth delay in the first week of administration of the micelle, whereas delayed growth of tumor was found between the first and the second week for mice injected with DOX-loaded PEG-PCL-PEG micelle. In addition, DOX-loaded micelle can reduce the injury to the liver. In the experiment of biodistribution, DOX-loaded micelle could prolong the retention time of DOX in blood. Base on these results, the biodegradable PEG-PCL-PEG triblock copolymer is potential in inhibiting the human breast cancerous tumor growth in nude mice.

並列關鍵字

manoparticle ； tumor inhibition effect ； micelle ； PEG-PCL-PEG

參考文獻

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