CN110772496A - 一种应用于肝癌介入治疗的紫杉醇纳米粒 - Google Patents
一种应用于肝癌介入治疗的紫杉醇纳米粒 Download PDFInfo
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Abstract
本发明为一种应用于肝癌介入治疗的紫杉醇纳米粒。采用溶酶挥发法制备装载紫杉醇的纳米粒,其对肝癌具有明显抗肿瘤效果。通过介入途径给予紫杉醇装载纳米粒,超选给药的前后端分别予以碘油封闭,进行夹心方式治疗,可以提高肝癌的治疗效果。
Description
【技术领域】
本发明属于药物剂型改进,为一种应用于肝癌介入治疗的紫杉醇纳米粒。
【背景技术】
肝癌是常见恶性肿瘤,恶性度高,治疗主要依靠以手术为主的综合治疗。由于肝癌起病隐匿,所以发现较晚,手术切除率低,而且术后复发率高。对于无法手术的肝癌患者,临床常采用常规介入和药物治疗,但总体效果并不理想。因此,开发更为有效的肝癌新治疗策略是一项重要而迫切的任务。
纳米药物是将药物制备成纳米尺度或应用纳米载体传输药物。纳米载体是指分散或装载有药物的各种纳米粒,目前已成为研究热点。与传统分子药物相比纳米药物的优点在于:纳米药物利用纳米颗粒的小尺寸效应,容易进入细胞而实现高疗效;纳米药物的比表面积大,链接或加载的功能基团或活性中心多;载体材料的性能优越,便于生物降解或吸收;纳米药物具有的多孔、中空、多层等结构特性,易于药物控制释放,改变药物在体内的半衰期,延长药物的作用时间;纳米药物通过结合抗体等配基制成靶向制剂,将药物主动输送到人体特定部位,实现低毒性和高疗效。纳米载体装载药物的技术已十分成熟,无论对于常用化疗药物单体,还是多药组合联合输送,相对于传统给药方式具有明显的优势。
给药途径是治疗成败的关键因素之一,介入治疗是肿瘤治疗的有效途径,超选给药的前后端分别予以碘油封闭,中间给予复合装载的纳米药物,累积的药物在局部高浓度释药,同时发挥其修饰的功能基团作用,这样夹心治疗法是一种理想的治疗模式。对于晚期的巨大肝癌患者,通过介入途径给予药物装载纳米粒,进行夹心方式的临床试验性治疗,开发疗效肯定的抗肿瘤新型纳米药物,具有广阔的应用前景。
【发明内容】
针对肝癌介入治疗效果的局限,本发明所述一种应用于肝癌介入治疗的紫杉醇纳米粒,能够通过夹心介入治疗法提高对肝癌的疗效。紫杉醇已应用于临床,将紫杉醇装载于纳米粒治疗肝癌在理论有基础,在临床应用上有前景。制备纳米载体的生物材料聚乳酸-羟基乙酸共聚物在体内生物降解为无毒的水和二氧化碳,美国FDA已批准其作为药物辅料用于临床。
采用单乳溶酶挥发法制备紫杉醇纳米粒。将一定质量紫杉醇溶于2.5%PLGA二氯甲烷溶液一倍体积,然后倒入1%PVA水溶液5倍体积,剧烈搅拌并超声乳化3min。生成的悬浊液持续磁力搅拌6h以挥发尽二氯甲烷,3000rpm离心弃上清,蒸馏水洗涤3遍,冷冻干燥后,纳米粒干粉4℃保存备用。
紫杉醇纳米粒载药率为4.50%,包封率为85.51%,呈光滑球形,粒径分布在100~500nm 之间,平均约300nm,模拟体外释药曲线呈双相,即在爆发释放之后为缓慢释放,1d内释放量占15%,14d内药物释放量约为30%。
紫杉醇纳米粒作用后,肝癌Huh7和HepG2细胞出现皱缩、崩解,细胞克隆形成能力降低,透射电镜观察到细胞对纳米粒的吞噬摄取,紫杉醇纳米粒组较药物单体作用更明显。Huh7 和HepG2细胞的接种率分别为87%和69%。细胞存活分析的结果指出与紫杉醇和紫杉醇纳米粒共培养的乏氧Huh7和HepG2细胞克隆形成能力较对照均显著降低,紫杉醇纳米粒的抗肿瘤作用较紫杉醇单体明显。紫杉醇纳米粒依靠被动靶向作用大量累积在Huh7移植瘤局部,具有明显增强的选择性杀伤作用。
Claims (4)
1.一种应用于肝癌介入治疗的纳米制剂,其特征在于:所属制剂包含紫杉醇和聚乳酸-羟基乙酸共聚物。其中聚乳酸-羟基乙酸共聚物为高分子生物载体材料。
2.紫杉醇纳米粒对肝癌具有明显抗肿瘤效果,通过介入途径给药,超选给药的前后端分别予以碘油封闭,进行夹心方式治疗,同时具有控释作用,可以提高疗效。
3.一种按照权利要求1所述的抗肝癌制剂,紫杉醇来源于植物提取或生物合成,聚乳酸-羟基乙酸共聚物为人工合成。
4.如权利要求1所述的药物配方中,紫杉醇和聚乳酸-羟基乙酸共聚物的质量比为1:4。制备方法:采用单乳溶酶挥发法制备紫杉醇纳米粒。将一定质量紫杉醇溶于2.5%PLGA二氯甲烷溶液一倍体积,然后倒入1%PVA水溶液5倍体积,剧烈搅拌并超声乳化3min。生成的悬浊液持续磁力搅拌6h以挥发尽二氯甲烷,3000rpm离心弃上清,蒸馏水洗涤3遍,冷冻干燥后,纳米粒干粉4℃保存备用。
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CN105055312A (zh) * | 2015-09-07 | 2015-11-18 | 苏州纳诺康生物技术有限公司 | 以聚乳酸-羟基乙醇酸共聚物为材料制备多西紫杉醇纳米载药颗粒的方法 |
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US20060034925A1 (en) * | 2004-04-02 | 2006-02-16 | Au Jessie L | Tumor targeting drug-loaded particles |
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