纳米尺度超声显影微囊的制备及性能表征

doi:10.7503/cjcu20130690

高等学校化学学报 ›› 2014, Vol. 35 ›› Issue (1): 191.doi: 10.7503/cjcu20130690

纳米尺度超声显影微囊的制备及性能表征

黄超凡¹, 曲冠雄¹, 魏振华¹, 许斌¹, 丁晶², 窦红静¹(), 孙康¹

1. 上海交通大学材料科学与工程学院, 金属基复合材料国家重点实验室, 上海 200240
2. 上海交通大学附属新华医院外科, 上海 200092

收稿日期:2013-07-19 出版日期:2014-01-10 发布日期:2013-09-29
作者简介:联系人简介: 窦红静, 女, 博士, 副教授, 博士生导师, 主要从事生物医用材料研究. E-mail:hjdou@sjtu.edu.cn
基金资助:
国家自然科学基金(批准号: 20904032, 21174082, 21374061)、教育部新世纪优秀人才支持计划(批准号: NCET-13-0360)、上海交通大学SMC-晨星青年学者奖励计划和上海交通大学金属基复合材料国家重点实验室开放基金资助

Fabrication and Medical Imaging of Ultrasonic Imaging Nanocaspsules^†

HUANG Chaofan, QU Guanxiong, WEI Zhenhua, XU Bin, DING Jing, DOU Hongjing^*(), SUN Kang

State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China

Received:2013-07-19 Online:2014-01-10 Published:2013-09-29
Contact: DOU Hongjing E-mail:hjdou@sjtu.edu.cn
Supported by:
† Supported by the National Natural Science Foundation of China(Nos.20904032, 21174082, 21374061), the Program for New Century Excellent Talents in University(No.NCET-13-0360), Shanghai Jiaotong University SMC-CHENXING Young Scholars Support Program, the State Key Loboratory of Metal Matrix Composities Operlab Fund

摘要/Abstract

摘要：

采用双乳液-溶剂挥发法制备了内部包封氟碳液体的聚乳酸-甲氧基聚乙二醇两嵌段共聚物(MePEG-b-PLA)基超声显影纳米微囊; 用2种不同嵌段比的MePEG-b-PLA共聚物研究共聚物组成与纳米囊性能的关系; 选用聚乙烯醇(PVA)、羧甲基葡聚糖(CMG)和壳聚糖(CS) 3种乳化剂对纳米囊表面进行亲水性修饰. 对所制备纳米囊的粒径、 Zeta电位、形貌和水溶液稳定性进行了表征. 结果表明, 利用质量分数为1%的PVA和质量分数为1%的CMG组成的复配乳化剂和m(MePEG)∶m(PLA)= 1∶3的聚合物制得的纳米囊的平均粒径为432.9 nm, 水溶液稳定性优良. 利用超声仪对纳米囊体外超声显影性能进行研究, 结果表明, 所得聚乳酸-甲氧基聚乙二醇纳米囊具有更好的中心成像区域灰度值和更持久的体外超声显影效果. 结合3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐(MTT)比色法研究证实该纳米囊具有低细胞毒性. 在超声影像学领域具有良好的应用前景.

关键词: 纳米微囊, 超声造影, 双乳液-溶剂挥发法, 聚乳酸-聚乙二醇基体, 乳化剂

Abstract:

Poly(lactic acid)-b-poly(ethylene glycol)(MePEG-b-PLA) based nanocapsules containing per-fluorohexane were fabricated through a double emulsion-solvent evaporation method. In the preparation, three kinds of hydrophilic polymers, i.e., poly(vinyl-alcohol)(PVA), chitosan(CS), and carboxymethyl dextran(CMG) were used as emulsifier or co-emulsifier to modify the surface of nanocapsules. Besides, two kinds of MePEG-b-PLA copolymers with different block length ratio were used as main shell composition to fabricate nanocapsules. Nanocapsule size, morphology, zeta potential, water stability of six nanocapsule samples fabricated by different polymers or emulsifiers were characterized by Malvern nanosizer analyzer, transmission electron microscope(TEM) and UV-Visible spectrophotometer(UV-Vis), respectively. The results showed that nanocapsules using 1%PVA+1%CMG as an emulsifier and MePEG-b-PLA[m(MePEG)∶m(PLA)=1∶3] as shell material had monodispersed small size and stable water property. These nanocapsules are not only in nanometer-scale but also possess favorable ultrasonic imaging property. Ultrasonic imaging property of nanocapsules was charaeterized using in vitro ultrasound tester and made a comparison with a commercialized ultrosonic imaging agent SonoVue^TM. The results demonstrated a brighter contrast scale and edurable ultrasonic property of MePEG-b-PLA nanocapsules. In addition, the cytotoxicity by incubating MePEG-b-PLA nanocapsules with rat liver cells line BRL-3A was characterized through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay. The results showed that the PLA-based nanocapsules imposed no significant inhibition effect on proliferation of BRL-3A cells.

Key words: Nanocapsule, Ultrasonic imaging, Double emulsion-solvent evaporation, Poly(lactic acid)-b-poly(ethylene glycol), Emulsifier

中图分类号:

TrendMD:

黄超凡, 曲冠雄, 魏振华, 许斌, 丁晶, 窦红静, 孙康. 纳米尺度超声显影微囊的制备及性能表征. 高等学校化学学报, 2014, 35(1): 191.

HUANG Chaofan, QU Guanxiong, WEI Zhenhua, XU Bin, DING Jing, DOU Hongjing, SUN Kang. Fabrication and Medical Imaging of Ultrasonic Imaging Nanocaspsules^†. Chem. J. Chinese Universities, 2014, 35(1): 191.

图/表 10

Scheme 1 Double emulsion/solvent evaporation process in the fabrication of nanocapsules

Table 1 Formula of nanocapsules different in emulsifier and mass fraction of MePEG and PLA

Sample	m(MePEG)∶m(PLA)	Mass fraction of emulsifier
FC1	1∶9	0.5%PVA
FC2	1∶9	1%PVA+1%CMG
FC3	1∶9	1%PVA
FC4	1∶9	0.5%PVA+0.5%CS
FC5	1∶3	1%PVA
FC6	1∶3	0.5%PVA+0.5%CS

Table 2 Average diameter of nanocapsule

Sample	Average diameter/nm	PDI
FC1	689.2	0.154
FC2	432.9	0.213
FC3	449.3	0.251
FC4	971.0	0.344
FC5	485.4	0.604
FC6	618.2	0.243

Fig.1 Nanoparticles diameter distribution of FC2

Fig.2 TEM images of FC2 saturated by phosphotungstic acid(A) and RuO4(B)

Fig.3 Normalized UV-Vis absorbance of FC1(a), FC2(b), FC3(c), FC4(d), FC5(e) and FC6(f) in water

Fig.4 Zeta Potentials of nanocapsules in water

Fig.5 Comparison of ultrasound contrast effect between FC2(A1,B1), SonoVueTM(A2,B2) and deionized water(A3,B3) at beginning(A) and 40 min(B)

Fig.6 Normalized grey scale of FC2(a) and SonoVueTM(b) relative to deionized water

Fig.7 Cytotoxicity profiles of BRL-3A cell, when incubated with FC2 nanocapsules as determined by MTT assay

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纳米尺度超声显影微囊的制备及性能表征

Fabrication and Medical Imaging of Ultrasonic Imaging Nanocaspsules^†

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纳米尺度超声显影微囊的制备及性能表征

Fabrication and Medical Imaging of Ultrasonic Imaging Nanocaspsules†

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Fabrication and Medical Imaging of Ultrasonic Imaging Nanocaspsules^†