中国组织工程研究

中国组织工程研究 ›› 2012, Vol. 16 ›› Issue (29): 5407-5411.doi: 10.3969/j.issn. 2095-4344.2012.29. 018

• 药物控释材料 drug delivery materials • 上一篇    下一篇

聚乳酸-羟基乙酸共聚物微球瘤内注射抑制荷人三阴性乳腺癌裸鼠移植瘤细胞的增殖

柯丽明，张秀娟，何以敉，林礼务，薛恩生，陈志奎   

  1. 福建医科大学附属协和医院超声科，福建省福州市 350001
  • 收稿日期:2012-01-24 修回日期:2012-04-05 出版日期:2012-07-15 发布日期:2012-07-15
  • 通讯作者: 陈志奎，博士，副主任医师，福建医科大学附属协和医院超声科暨福建省超声医学研究所，福建省福州市 350001 jimchen2003@ 163.com
  • 作者简介:柯丽明★，女，1985年生，福建省莆田市人，福建医科大学在读硕士，医师，主要从事乳腺癌超声诊断与介入治疗的研究。 woshikeliming@163.com

Inhibitory effect of poly (lactic-co-glycolic acid) microspheres containing docetaxel intratumoral injection on the proliferation of human triple negative breast cancer xenograft in nude mice

Ke Li-ming, Zhang Xiu-juan, He Yi-mi, Lin Li-wu, Xue En-sheng, Chen Zhi-kui   

  1. Department of Ultrasound, Union Hospital, Fujian Medical University, Fuzhou 350001, Fujian Province, China
  • Received:2012-01-24 Revised:2012-04-05 Online:2012-07-15 Published:2012-07-15
  • Contact: Chen Zhi-kui, Doctor, Associate chief physician, Department of Ultrasound, Union Hospital, Fujian Medical University, Fuzhou 350001, Fujian Province, China jimchen2003@ 163.com
  • About author:Ke Li-ming★, Studying for master’s degree, Physician, Department of Ultrasound, Union Hospital, Fujian Medical University, Fuzhou 350001, Fujian Province, China woshikeliming@ 163.com

PDF

539

被引次数

5

摘要：

背景：通过超声引导，将抗肿瘤药物缓释剂注射到肿瘤局部进行间质化疗，可提高抗肿瘤效果，并且减轻全身毒副作用。
目的：观察超声引导下瘤内注射多西他赛聚乳酸-羟基乙酸微球对荷人三阴性乳腺癌裸鼠移植瘤增殖的抑制作用。
方法：采用乳化溶剂挥发法制备多西他赛聚乳酸-羟基乙酸微球，扫描电镜观察微球的表面形态及粒径，高效液相色谱法测定包封率、载药率及体外释放情况。建立荷人三阴性乳腺癌裸鼠移植瘤模型，随机分为5组：模型组无处理；微球组在肿瘤内注射空白聚乳酸-羟基乙酸微球1次；多西他赛瘤内注射组在肿瘤内注射多西他赛注射液(多西他赛剂量为10 mg/kg)，每10 d给药1次，连续4次；多西他赛聚乳酸-羟基乙酸共聚物微球低剂量组在肿瘤内注射载药微球(多西他赛剂量为20 mg/kg)1次；多西他赛聚乳酸-羟基乙酸共聚物微球高剂量组在肿瘤内注射载药微球(多西他赛剂量为40 mg/kg)1次。
结果与结论：多西他赛聚乳酸-羟基乙酸微球平均粒径23.1 μm，包封率为96.3%，载药率为4.82%，40 d累积释放药物85.7%。超声引导下多西他赛聚乳酸-羟基乙酸微球瘤体内注射具有明显的抗肿瘤作用，高剂量组抑瘤率达65.7%，彩色多普勒超声见肿瘤血流信号明显减少，病理学检查见肿瘤组织大片坏死，提示超声引导下瘤内注射多西他赛聚乳酸-羟基乙酸微球可明显抑制荷人三阴性乳腺癌裸鼠移植瘤增殖。

关键词: 乳酸-羟基乙酸, 超声, 微球, 多西他赛, 乳腺癌, 生物材料

Abstract:

BACKGROUND: Under ultrasound guidance, intratumoral injection of sustained-released chemotherapeutics for tumor interstitial chemotherapy can improve antitumor and decrease systemic toxicity and side effects.
OBJECTIVE: To investigate the inhibitory effect of poly (lactic-co-glycolic acid) (PLGA) microspheres containing docetaxel intratumoral injection under ultrasound guidance on the proliferation of human triple negative breast cancer xenograft.
METHODS: Sustained-release PLGA microspheres containing docetaxel was prepared by solvent evaporation method. The morphology and particle size were observed by scanning electron microscope. The drug loading rate, entrapment efficiency and in vitro release were examined by high performance liquid chromatography. The human triple negative breast cancer-bearing nude mouse model was established and divided into five groups: model group (with no treatment), microspheres group (injected blank PLGA microspheres), docetaxel intratumoral injection group (injected 10 mg/kg docetaxel and administrated once every 10 days for 40 days continuously), PLGA microspheres containing docetaxel low-dose group (injected drug-released microspheres intratumorally: 20 mg/kg docetaxel one time) and PLGA microspheres containing docetaxel high-dose group (injected 40 mg/kg docetaxel one time)
RESULTS AND CONCLUSION: The mean particle size of prepared PLGA microspheres containing docetaxel was detected as 23.1 μm with an optimal entrapment efficiency of 96.3%, drug loading rate of 4.82%, and cumulative release drug rate of 85.7% within 40 days. Under ultrasound guidance, intratumoral injection of PLGA microspheres containing docetaxel displayed a potent antitumor effect on human triple negative breast cancer xenograft. And the tumor inhibition rate of the high-dose group had reached 65.7%. Color Doppler ultrasound showed the tumor blood supply was significantly decreased. Pathological examination indicated that the tumor tissues were found a great of putrescence. These findings suggest that interstitial chemotherapy by using ultrasound-guided intratumoral injection of PLGA microspheres containing docetaxel can significantly inhibit the proliferation of human triple negative breast cancer xenograft.

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