Formulation and characterization of echogenic lipid-Pluronic nanobubbles.
Formulation and characterization of echogenic lipid-Pluronic nanobubbles.
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DOI：
10.1021/mp9001816
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发表时间：
2010-02-01
影响因子：
4.9
通讯作者：
Exner AA
中科院分区：
文献类型：
--
作者：
Krupka TM;Solorio L;Wilson RE;Wu H;Azar N;Exner AA
微泡造影剂的出现增强了超声作为医学成像手段的能力，并促进了超声介导的药物和基因传递的创新策略。虽然利用微泡作为载体在癌症治疗中取得了令人鼓舞的结果，但它们的适用性受到了大尺寸的限制，这通常将它们限制在血管系统中。为了提高多功能对比度和传递能力，关键是在不降低回声的情况下将气泡尺寸减小到纳米范围。在这项工作中，我们提出了一种新的策略，通过在配方中加入表面活性剂Pluronic，一种环氧乙烷-环氧丙烷-环氧乙烷的三嵌段共聚物，来配制纳米级的回声脂泡。5种Pluronics(L31、L61、L81、L64和P85)在脂膜水化前后和加入全氟化碳气体之前加入到脂膜中，分子量范围为1100~4600 Da。结果表明，Pluronic与脂质的相互作用显著减小了气泡的尺寸。在受试处方中，以Pluronic L61制成的泡泡最小，平均流体力学直径为207.9±74.7 nm，而对照泡泡的平均直径为880.9±127.6 nm。Pluronic L81还显著减小了气泡大小，为406.8±21.0 nm。我们的结论是，Pluronic在控制脂肪泡大小方面是有效的，Pluronic MW、亲水性-亲脂性平衡(HLB)和Pluronic/Latio比率是决定泡泡大小的关键因素。最重要的是，我们的结果表明，尽管气泡是纳米级的，但它们的稳定性以及体内外回声能力都没有受到影响。由此产生的纳米气泡可能更适合于对比剂增强的肿瘤成像和随后的治疗输送。
The advent of microbubble contrast agents has enhanced the capabilities of ultrasound as a medical imaging modality and stimulated innovative strategies for ultrasound-mediated drug and gene delivery. While the utilization of microbubbles as carrier vehicles has shown encouraging results in cancer therapy, their applicability has been limited by a large size which typically confines them to the vasculature. To enhance their multifunctional contrast and delivery capacity, it is critical to reduce bubble size to the nanometer range without reducing echogenicity. In this work, we present a novel strategy for formulation of nanosized, echogenic lipid bubbles by incorporating the surfactant Pluronic, a triblock copolymer of ethylene oxide copropylene oxide coethylene oxide into the formulation. Five Pluronics (L31, L61, L81, L64 and P85) with a range of molecular weights (Mw: 1100 to 4600 Da) were incorporated into the lipid shell either before or after lipid film hydration and before addition of perfluorocarbon gas. Results demonstrate that Pluronic–lipid interactions lead to a significantly reduced bubble size. Among the tested formulations, bubbles made with Pluronic L61 were the smallest with a mean hydrodynamic diameter of 207.9 ± 74.7 nm compared to the 880.9 ± 127.6 nm control bubbles. Pluronic L81 also significantly reduced bubble size to 406.8 ± 21.0 nm. We conclude that Pluronic is effective in lipid bubble size control, and Pluronic Mw, hydrophilic–lipophilic balance (HLB), and Pluronic/ lipid ratio are critical determinants of the bubble size. Most importantly, our results have shown that although the bubbles are nanosized, their stability and in vitro and in vivo echogenicity are not compromised. The resulting nanobubbles may be better suited for contrast enhanced tumor imaging and subsequent therapeutic delivery.
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影响因子：
2.9
作者：
Crowder, KC;Hughes, MS;Wickline, SA
通讯作者：
Wickline, SA
DOI：
10.1109/58.741536
发表时间：
1999-01-01
影响因子：
3.6
作者：
Dayton, PA;Morgan, KE;Ferrara, KW
通讯作者：
Ferrara, KW
影响因子：
3.7
作者：
Batrakova, EV;Han, HY;Kabanov, AV
通讯作者：
Kabanov, AV
影响因子：
18.3
作者：
Ferrara, Katherine W.;Borden, Mark A.;Zhang, Hua
通讯作者：
Zhang, Hua
影响因子：
2.9
作者：
Bouakaz, A;Frinking, PJA;Bom, N
通讯作者：
Bom, N