本文關鍵詞： 阿齊他賽 膠束 載藥量 釋放 模型 抗腫瘤活性　出處：《中國藥學雜志》2015年19期 　論文類型：期刊論文

【摘要】：目的制備阿齊他賽聚乙二醇單甲醚-聚乳酸雙嵌段共聚物(m PEG-PLA)聚合物膠束,考察載藥膠束的理化性質并研究其體外抗腫瘤活性。方法采用薄膜分散法制備阿齊他賽聚乙二醇單甲醚-聚乳酸雙嵌段共聚物聚合物膠束,透射電鏡觀察載藥膠束的形態(tài),激光粒度分析儀測定載藥膠束的粒徑和Zeta電位,考察載藥膠束的工藝重現性和復溶穩(wěn)定性,HPLC測定膠束載藥量和包封率,透析法考察載藥膠束的體外釋放行為,并對釋放曲線進行數學模型擬合,增殖抑制實驗和周期阻滯實驗評價其體外抗MCF-7腫瘤細胞活性。結果本實驗成功制備了阿齊他賽聚合物膠束,其外觀形態(tài)呈球形,粒徑為24.50 nm,粒徑多分散指數為0.117,Zeta電位為-10.06 m V,載藥量為(16.00±0.15)%,包封率為(95.80±0.10)%,制備工藝重現性良好,載藥膠束凍干制劑復溶后6 h之內保持穩(wěn)定,載藥膠束體外釋放行為符合雙相動力學模型,載藥膠束在體外能明顯抑制MCF-7乳腺癌細胞的增殖,并誘導MCF-7細胞產生明顯的G2/M周期阻滯和細胞凋亡。結論本實驗制備了阿齊他賽聚乙二醇單甲醚-聚乳酸雙嵌段共聚物聚合物膠束,膠束制備工藝簡單,理化性質符合后續(xù)研究要求,在體外顯示了良好的抗腫瘤作用,具有良好應用前景。
[Abstract]:Objective to prepare azetaxel poly (ethylene glycol) -poly (lactic acid) diblock copolymer (mPEG-PLA) polymer micelles. The physicochemical properties of drug-loaded micelles and their antitumor activities in vitro were investigated. Methods Acetaxel poly (ethylene glycol) -poly (lactic acid) diblock copolymer polymer micelles were prepared by thin-film dispersion method. The morphology of drug-loaded micelles was observed by transmission electron microscope, the particle size and Zeta potential of drug-loaded micelles were measured by laser particle size analyzer, and the reproducibility and resolubility stability of drug-loaded micelles were investigated. The drug loading and encapsulation efficiency of micelle were determined by HPLC. The release behavior of drug loaded micelle in vitro was investigated by dialysis, and the release curve was fitted by mathematical model. Proliferation inhibition assay and cycle arrest assay were used to evaluate the antitumor activity of Acetaxel in vitro. Results Acetaxel polymer micelles were successfully prepared in this experiment and their appearance was spherical. The particle size was 24.50 nm, the particle size multiple dispersion index was 0.117 渭 g Zeta potential was -10.06 MV, and the drug loading capacity was 16.00 鹵0.15 渭 m 路mol ~ (-1) 路L ~ (-1) 路L ~ (-1) 路min ~ (-1). The entrapment efficiency was 95.80 鹵0.10%, the preparation process was reproducible, the drug delivery micelle was stable within 6 h after resolution, and the release behavior of the drug carrier micelle in vitro was in accordance with the biphasic kinetic model. Drug carrier micelles could significantly inhibit the proliferation of MCF-7 breast cancer cells in vitro. The G _ 2 / M cycle arrest and apoptosis were induced in MCF-7 cells. Conclusion Acetaxel poly (ethylene glycol) -poly (lactic acid) diblock copolymer polymer micelles were prepared in this experiment. The micelle preparation process is simple and the physicochemical properties meet the requirements of follow-up studies. It has shown good antitumor effect in vitro and has a good application prospect.
【作者單位】： 中國醫(yī)學科學院北京協和醫(yī)學院藥物研究所天然藥物活性物質與功能國家重點實驗室;中國醫(yī)學科學院北京協和醫(yī)學院藥物研究所藥物研究所藥物制劑研究室;中國醫(yī)學科學院北京協和醫(yī)學院藥物研究所天然藥物化學研究室;
【基金】：國家“重大新藥創(chuàng)制”科技重大專項資助項目(2012ZX09301002-001-008)
【分類號】：R943;R96
【正文快照】： 紫杉醇和多西紫杉醇是目前較為有效的抗腫瘤藥物,抗腫瘤譜廣,臨床上廣泛用于乳腺癌和卵巢癌的治療,但在臨床使用過程中發(fā)現紫杉醇及多西紫杉醇對原發(fā)及繼發(fā)性紫杉醇腫瘤耐藥病人的化療均無效,其重要原因之一就是患者腫瘤細胞中P-糖蛋白(P-gp)過度表達[1],導致藥物外排增加,細

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