新型纳米级超声造影剂的制备及其特性

doi:10.6040/j.issn.1671-7554.0.2016.728

摘要/Abstract

摘要： 目的制备新型纳米级脂质超声造影剂(UCAs),并对其基本特性及显影效果进行研究。方法采用机械振荡法制备脂质UCAs,针对制备过程中3个主要影响因素,设置正交试验,筛选最优制备条件,并在此条件下制备纳米级UCAs,检测其粒径、分散度、Zeta电位、稳定性及体外增强显影效果。结果正交试验结果显示,机械振荡时间对粒径影响有统计学意义(P<0.05),纳米级UCAs最优制备条件为:DPPA量为0.5 mL,机械振荡时间为90 s, 离心时间为3 min;在此条件下制备出的纳米级UCAs平均粒径为(313.20±6.90)nm,分散度为0.15,Zeta电位为-12.40 mV,体外增强显影效果与声诺维相比差异无统计学意义(t=2.02, P>0.05)。4 ℃冰箱保存20 h后观察,该造影剂基本特性无明显改变。结论制备的纳米级UCAs粒径小,分散均一,性质稳定,具备良好的显影能力,且易于修饰,为进一步载药或构建纳米粒复合体等方面的研究奠定了基础。

关键词: 超声造影剂, 纳米级, 脂质, 显影, 纳米颗粒

Abstract: Objective To prepare lipid nanoscaled ultrasound contrast agents(UCAs), and to explore their physiochemical properties. Methods Orthogonal test was used to screen out the optimal condition for preparation aiming at three mainly factors. Amalgamator was applied to fabricate the lipid nanoscaled UCAs. The morphology, diameter, polydispersity index(P.I), zeta potential and stability of nanoscaled UCAs were assessed. The enhancement effect of nanoscaled UCAs in vitro was also detected. Results The results of orthogonal test indicated that the oscillation time had a significant effect on the diameter of nanoscaled UCAs(P<0.05). The optimal condition of preparation was as follows: the amount of DPPA was 0.5 mL, oscillation time was 90 s, and centrifugation time was 3 min. The mean diameter and P.I of the nanoscaled UCAs fabricated under the optimal condition was(313.20±6.90)nm and 0.15, respectively. The Zeta potential was -12.40 mV. There was no significant difference in the enhancement effect between the nanoscaled UCAs and SonoVue in vitro(t=2.02, P>0.05). The basic physical characteristics of the nanoscaled UCAs remained unchanged after being stored in 4 ℃ refrigerator for 20 hours. Conclusion Nanoscaled UCAs with smaller diameter and good stability were successfully fabricated. All these characteristics indicate a promising future in targeted molecular imaging and drug or gene delivery.

Key words: Nanoscaled, Nanoparticle, Ultrasound contrast agents, Lipid, Enhancement effect

中图分类号:

R445.1

段素娟,时丹丹,商蒙蒙,郭鲁,孙霄,孟冬,李杰. 新型纳米级超声造影剂的制备及其特性[J]. 山东大学学报（医学版）, 2017, 55(4): 50-54.

DUAN Sujuan, SHI Dandan, SHANG Mengmeng, GUO Lu, SUN Xiao, MENG Dong, LI Jie. Preparation and characteristics of novel nanoscaled ultrasound contrast agents[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(4): 50-54.

参考文献

[1] 杨恒丽, 蔡文斌, 张莉, 等. 纳米级分子靶向超声造影剂的制备及其体外肿瘤靶向性实验研究[J].中国超声医学杂志, 2016, 32(4): 367-370. YANG Hengli, CAI Wenbin, ZHANG Li, et al. Preparation of nanoscale molecular targeting ultrasound contrast agents and its tumor targeting experiment in vitro[J]. Chin J Ultrasound in Med, 2016, 32(4): 367-370.
[2] Qin J, Wang TY, Willmann JK. Sonoporation: applications for cancer therapy[J]. Adv Exp Med Biol, 2016, 880: 263-291. doi: 10.1007/978-3-319-22536-4_15.
[3] Tong HP, Wang LF, Guo YL, et al. Preparation of protamine cationic nanobubbles and experimental study of their physical properties and in vivo contrast enhancement[J]. Ultrasound Med Biol, 2013, 39(11): 2147-2157.
[4] Kiessling F, Fokong S, Koczera P, et al. Ultrasound microbubbles for molecular diagnosis, therapy, and theranostics[J]. J Nucl Med, 2012, 53(3): 345-348.
[5] Tian J, Yang F, Cui H, et al. A novel approach to making the gas-filled liposome real: based on the interaction of lipid with free nanobubble within the Solution[J]. ACS Appl Mater Inte, 2015, 7(48): 579-584.
[6] Chen WT, Kang ST, Lin JL, et al. Targeted tumor theranostics using folate-conjugated and camptothecin-loaded acoustic nanodroplets in a mouse xenograft model[J]. Biomaterials, 2015, 53: 699-708.
[7] Pereea RH, Solorio L, Wu H, et al. Nanobubble ultrasound contrast agents for enhanced delivery of thermal sensitizer to tumors undergoing radiofrequency ablation[J]. Pharmacol Res, 2014, 31(6): 1407-1417.
[8] Figueiredo M, Esenaliev R. PLGA nanoparticles for ultrasound-mediated gene delivery to solid tumors[J]. J Drug Deliv, 2012, 2012: 767839. doi: 10.1155/2012/767839.
[9] Xing Z, Wang J, H Ke, et al. The fabrication of novel nanobubble ultrasound contrast agent for potential tumor imaging[J]. Nanotechnology, 2010, 21(14): 145607.doi: 10.1088/0957-4484/21/14/145607.
[10] Zhou QL, Chen ZY, Wang YX, et al. Ultrasound-mediated local drug and gene delivery using nanocarriers[J] , Biomed Res Int, 2014, 2014: 963891. doi: 10.1155/2014/963891.
[11] Zhang M, Yu WZ, Shen XT, et al. Advanced interfere treatment of diabetic cardiomyopathy rats by a FGF-loaded Heparin-modified microbubbles and UTMD technique[J]. Cardiovasc Drug Ther, 2016,30(3): 247-261.
[12] Chen H, Hwang JH. Ultrasound-targeted microbubble destruction for chemotherapeutic drug delivery to solid tumors[J]. J Ther Ultrasound, 2013, 1: 10. doi: 10.1186/2050-5736-1-10.
[13] Gauthier M, Yin Q, Cheng J, et al. Design of albumin-coated microbubbles loaded with polylactide nanoparticles[J]. J Ultras Med, 2015, 34(8): 1363-1372.
[14] Miller AD. Lipid-based nanoparticles in cancer diagnosis and therapy[J]. J Drug Deliv, 2013, 2013: 165981. doi: 10.1155/2013/165981.
[15] Rosen JE, Chan L, Shieh DB, et al. Iron oxide nanoparticles for targeted cancer imaging and diagnostics[J]. Nanomedicine, 2012, 8(3): 275-290.
[16] 王平, 尹庭辉, 郑荣琴. 新型纳米微泡超声造影剂的制备及超声显像研究[J]. 中山大学学报(医学科学版), 2011, 32(3): 327-330. WANG Ping, YIN Tinghui, ZHENG Rongqin. Preparation and ultrasonic imaging of novel nanoscale bubble ultrasound contrast agent[J]. J Sun Yat-Sen Univ Med Sci, 2011, 32(3): 327-330.
[17] Pan TL, Wang PW, Al-Suwayeh SA, et al. Toxicological effects of cationic nanobubbles on the liver and kidneys: biomarkers for predicting the risk[J]. Food Chem Toxicol, 2012, 50(11): 3892-3901.
[18] Wang TL, Sung CT, Aljuffali IA, et al. Cationic surfactants in the form of nanoparticles and micelles elicit different human neutrophil responses: a toxicological study[J]. Colloids Surf B Biointerfaces, 2014, 114: 334-341.
[19] 张亚萍, 冉海涛. 脂质微泡与PLGA纳米粒复合体的制备原理分析[J]. 中华临床医师杂志(电子版), 2013, 7(9): 133-135. ZHANG Yaping, RAN Haitao. Analysis of the preparation principle of the complex of lipid ultrasound microbubbles and PLGA nanoparticles[J]. Chin J Clinicians(Electronic Edition), 2013, 7(9): 133-135.
[20] Perera RH, Hernandez C, Zhou H, et al. Ultrasound imaging beyond the vasculature with new generation contrast agents[J]. Wires Nanomed Nanobi, 2015, 7(4): 593-608.
[21] Cai WB, Yang HL, Zhang J, et al. The optimized fabrication of nanobubbles as ultrasound contrast agents for tumor imaging[J]. Sci Rep, 2015, 5: 13725. doi: 10.1038/srep13725.

相关文章 15

[1]	宋轲,牟宗友,翟申浩,牛闯,郭亚琪,张腾腾,任雪冰,刘培来. 布比卡因脂质体在全膝关节置换术后的镇痛疗效[J]. 山东大学学报 (医学版), 2026, 64(2): 111-117.
[2]	李习平,邱梅,黄瑞峰,林慧慧,刘丝丝,罗鸿莹,王宇月,王敏,杨晓彤. 基于脂质沉积抑制-代谢清除协同效应的黄连素抗动脉粥样硬化机制研究进展[J]. 山东大学学报 (医学版), 2025, 63(9): 77-83.
[3]	杜艾家,张曼,陈鹤,王丽新,尚应殊. 微小RNA-1270靶向调控血管生成素样蛋白7抑制巨噬细胞炎症和脂质蓄积[J]. 山东大学学报 (医学版), 2025, 63(2): 1-9.
[4]	巩洁,于淼,李秀勇,陈颖,徐倩茹,李梅娟,李艺彤,刘秀美. 基于上转换纳米粒子多糖探针的构建及其在肿瘤成像中的应用[J]. 山东大学学报 (医学版), 2025, 63(11): 18-26.
[5]	张琪晨,康随芳,殷钏杰,肖娟,马广凤,曹媛,陈国玲. 强脉冲光治疗对脂质异常型干眼睑板腺及泪膜脂质层的影响[J]. 山东大学学报 (医学版), 2024, 62(4): 54-60.
[6]	潘庆鑫,张越,刘松涛,陈海燕,王哲. 骨破坏、多尿-Paget骨病合并脂质肉芽肿病1例[J]. 山东大学学报 (医学版), 2024, 62(1): 115-119.
[7]	李晓梅,梁婷,张超,曹慧,侯桂华. 抑制T细胞CDK9对TLR5靶向监测同种异体移植排斥的影响[J]. 山东大学学报 (医学版), 2018, 56(7): 1-6.
[8]	赵姗姗,李晓梅,梁婷,张超,宋静,侯桂华. 自噬对¹²⁵I-anti-TLR5同种移植排斥靶向显像的影响[J]. 山东大学学报（医学版）, 2017, 55(9): 46-52.
[9]	张新科,陈英,李鹏,陈洪元,黄桂华. PEG包衣左氧氟沙星脂质体的制备及性质[J]. 山东大学学报（医学版）, 2017, 55(8): 42-47.
[10]	王丹,亓恒涛,孙书珍. 原发性肾病综合征儿童颈动脉结构和功能改变[J]. 山东大学学报（医学版）, 2016, 54(5): 88-91.
[11]	董兆静，尚倩雯，郭春，张利宁，王群. RNA干扰PDCD4基因表达对巨噬细胞脂质沉积的影响[J]. 山东大学学报（医学版）, 2014, 52(4): 18-21.
[12]	江娜. 奥沙拉嗪联合甘草酸二铵对溃疡性结肠炎患者脂质过氧化损伤和IL-1β水平的影响[J]. 山东大学学报(医学版), 2011, 49(9): 114-116.
[13]	解斐1，张栋2，刘天华1，黄桂华2. 氯诺昔康固体脂质纳米粒的实验研究[J]. 山东大学学报(医学版), 2010, 48(4): 155-159.
[14]	李小海1，何建行1，陈萍2，魏献忠2，张贵平3，花宁4. 兔下肢局部注射氟尿嘧啶脂质体的淋巴靶向示踪[J]. 山东大学学报(医学版), 2010, 48(1): 78-81.
[15]	孙庆雪，黄桂华，邵伟. 褪黑素脂质体的制备及理化性质研究[J]. 山东大学学报(医学版), 2010, 48(1): 159-163.

多维度评价

Viewed

Full text

Abstract

Cited

Shared

Discussed