秋水仙碱纳米控释微粒抗肿瘤的实验研究

目的：研究不溶于水的植物性抗癌药秋水仙碱纳米控释静脉注射微粒的制备工艺及其体内外抗肿瘤作用。方法：以聚乳酸－聚乙醇酸共聚物（PLGA）作为基质材料，采用超声乳化－溶剂挥发法制备PLGA包载秋水仙碱的纳米级微粒（NP）。借助扫描电镜观察PLGA－秋水仙碱－NP微粒形态，通过激光光散射实验测定纳米微粒的粒径分布。利用高效液相色谱（HPLC）测定纳米微粒制剂的载药率，以MTT方法做体外杀伤癌细胞实验，进行不同剂量，给药频度条件下体内抑瘤实验。结果：经电镜观察PLGA－秋水仙碱－NP为表现光滑的球形微粒，粒径分布平均值是104．9nm，呈正态分布，PLGA－秋水仙碱－NP载药率为33．0％。体外MTT实验提示纳米粒子粒子与裸药作用相同且显著控释，体内抑制实验表明：控释制剂间隔给药疗效优于包载药物每日给药的疗效，量－效关系, 毒性显著减低，经静脉途径试用无任何不良反应。结论：PLGA纳米粒子可以作为抗肿瘤药物秋水仙碱的有效载体，并可在不添加助溶剂等前提下成功制备其静脉注射剂型，实现药物控制释放并减低毒性，发挥药物更佳的抗肿瘤作用。

Experimental Study of Colchicine Nanoparticle Control-releasing on Tumor

Objective: To investigate the preparation technics and anti-tumor effects both in vitro and in vivo of a novel nanosphere control-releasing preparation of colchicines (an water-insoluble anti-cancer drug) by intravenous injection. Methods: With polylactate-poly ethanol acid copolymer (PLGA) as marix materials, we adopted ultrasound emulsification/dissolvent volatilization method to prepare PLGA enveloped colchicines of nano-particles (NP), proceeding the appearance signs of PLGA- colchicine-NP, making use of scanning electricity microscopy to look into the morphology of nanoparticles through laser optical scattering experiment and determine its diameter distribution. We carry out the drug-carrying coefficient (ratio) of the nanoparticles by means of HPLC, use MTT test to do the cancer cell bloodsheding test in vitro, and pursue the anti-tumor effects of different dosages, frequencies of taking medicine, and preparation techinics circumstances. Results: The average value of particle diameter was 104.9 nm with a normality distribution, and the drug-carrying amount of PLGA-colchicine-NP was 33.0% . NP had the same anti-cancer effect as unenveloped drug in vitro tests. Nanoparticles showed an apparent dosage-efficacy relationship, and the efficacy by interval drug delivery was better than unenveloped drug by per diem drug delivery. The toxicity decreased significantly. No mal-reaction was found by intravenous injection. Conclusion: Nanoparticles may serve as availability carrier of colchicines, and can be succeessesfuly used in the preparation of its intravenous injection dose. It can play more efficient role of anti-cancer effects of the drug.