Tailoring the size of ultrasound responsive lipid-shelled nanodroplets by varying production parameters and environmental conditions.
Tailoring the size of ultrasound responsive lipid-shelled nanodroplets by varying production parameters and environmental conditions.
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DOI：
10.1016/j.ultsonch.2021.105482
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发表时间：
2021-05
影响因子：
8.4
通讯作者：
Carugo D
中科院分区：
文献类型：
--
作者：
Ferri S;Wu Q;De Grazia A;Polydorou A;May JP;Stride E;Evans ND;Carugo D
增加 PFP 的体积浓度会导致脂质包被的 PFP ND 尺寸增加。增加超声处理强度和时间导致 ND 尺寸减小。 ND 涂层可以用亲脂性荧光团标记，而不影响整体 ND 尺寸。 ND 在 4°C 下稳定 1 周，在 37°C 下稳定 110 分钟。超声波（0.5 MHz，2–4 MPa）导致模拟组织模型内的 ND 蒸发。液体全氟化碳纳米液滴 (ND) 是超声介导的治疗和诊断应用中微泡 (MB) 的有吸引力的替代品。 ND 尺寸和尺寸分布对其体内行为有很大影响，包括外渗效率、循环时间和对超声刺激的反应。因此，需要找到在制造过程中定制 ND 尺寸和尺寸分布的方法。在本研究中，磷脂包被的 ND 包含由 DSPC/PEG40（1,2-二硬脂酰基-sn-甘油-3-磷酸胆碱和聚氧乙烯 (40) 硬脂酸酯，摩尔比为 9:1）外壳稳定的全氟正戊烷 (PFP) 核，通过超声处理在磷酸盐缓冲盐水 (PBS) 中生产。研究了以下与生产相关的参数对 ND 尺寸的影响：PFP 浓度、超声处理的功率和持续时间，以及亲脂性荧光染料的掺入。 ND 稳定性也在 4°C 和 37°C 下进行了评估。当采用 6 s 和 15% 占空比的超声脉冲时，将 PBS 中 PFP 的体积浓度从 5% v/v 增加到 15% v/v 导致 ND 直径从 215.8 ± 16.8 nm 增加到 408.9 ± 171.2 nm。超声处理强度从 48 W 增加到 72 W（PBS 中含有 10% PFP v/v）导致 ND 尺寸从 354.6 ± 127.2 nm 减小到 315.0 ± 100.5 nm。将超声处理时间从 20 秒增加到 40 秒（使用占空比为 30% 的脉冲超声处理）不会导致 ND 尺寸（在 278–314 nm 范围内）发生显着变化；然而，当时间增加到 60 秒时，平均 ND 直径减小到 249.7 ± 9.7 nm，与研究的其他实验条件相比，其标准偏差也显着降低（即 9.7 nm 与 > 49.4 nm）。添加不同摩尔比的荧光染料 DiI 不会影响 ND 粒径分布。 ND 在 4°C 下稳定长达 6 天，在 37°C 下稳定长达 110 分钟；然而，在 37°C 下 40 分钟后观察到了 ND 到 MB 相变的一些证据。最后，在治疗性超声暴露条件下（超声频率：0.5 MHz，声压：2-4 MPa，脉冲重复频率：100 Hz），使用模拟组织流动模型演示了 ND 向 MB 的相变。
Increasing the volumetric concentration of PFP led to an increase in the size of lipid-coated PFP NDs. Increasing sonication intensity and time led to a decrease in ND size. The ND coating layer can be labelled with lipophilic fluorophores without affecting the overall ND size. NDs were stable at 4 °C for one week, and at 37 °C for 110 min. Ultrasound (0.5 MHz, 2–4 MPa) caused vaporisation of NDs within a tissue-mimicking phantom. Liquid perfluorocarbon nanodroplets (NDs) are an attractive alternative to microbubbles (MBs) for ultrasound-mediated therapeutic and diagnostic applications. ND size and size distribution have a strong influence on their behaviour in vivo, including extravasation efficiency, circulation time, and response to ultrasound stimulation. Thus, it is desirable to identify ways to tailor the ND size and size distribution during manufacturing. In this study phospholipid-coated NDs, comprising a perfluoro-n-pentane (PFP) core stabilised by a DSPC/PEG40s (1,2-distearoyl-sn-glycero-3-phosphocholine and polyoxyethylene(40)stearate, 9:1 molar ratio) shell, were produced in phosphate-buffered saline (PBS) by sonication. The effect of the following production-related parameters on ND size was investigated: PFP concentration, power and duration of sonication, and incorporation of a lipophilic fluorescent dye. ND stability was also assessed at both 4 °C and 37 °C. When a sonication pulse of 6 s and 15% duty cycle was employed, increasing the volumetric concentration of PFP from 5% to 15% v/v in PBS resulted in an increase in ND diameter from 215.8 ± 16.8 nm to 408.9 ± 171.2 nm. An increase in the intensity of sonication from 48 to 72 W (with 10% PFP v/v in PBS) led to a decrease in ND size from 354.6 ± 127.2 nm to 315.0 ± 100.5 nm. Increasing the sonication time from 20 s to 40 s (using a pulsed sonication with 30% duty cycle) did not result in a significant change in ND size (in the range 278–314 nm); however, when it was increased to 60 s, the average ND diameter reduced to 249.7 ± 9.7 nm, which also presented a significantly lower standard deviation compared to the other experimental conditions investigated (i.e., 9.7 nm vs. > 49.4 nm). The addition of the fluorescent dye DiI at different molar ratios did not affect the ND size distribution. NDs were stable at 4 °C for up to 6 days and at 37 °C for up to 110 min; however, some evidence of ND-to-MB phase transition was observed after 40 min at 37 °C. Finally, phase transition of NDs into MBs was demonstrated using a tissue-mimicking flow phantom under therapeutic ultrasound exposure conditions (ultrasound frequency: 0.5 MHz, acoustic pressure: 2–4 MPa, and pulse repetition frequency: 100 Hz).
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影响因子：
3.5
作者：
Sheeran PS;Matsunaga TO;Dayton PA
通讯作者：
Dayton PA
影响因子：
2.8
作者：
Dayton, Paul A.;Zhao, Shukui;Ferrara, Katherine W.
通讯作者：
Ferrara, Katherine W.
基于聚乙二醇化 PLGA 的相移纳米液滴结合聚焦超声用于大鼠血脑屏障开放
影响因子：
--
作者：
Zhang X;Hu J;Zhao G;Huang N;Tan Y;Pi L;Huang Q;Wang F;Wang Z;Wang Z;Cheng Y
通讯作者：
Cheng Y
影响因子：
3.2
作者：
Sheeran PS;Dayton PA
通讯作者：
Dayton PA
用作抗癌药物载体的相移纳米乳液中的微泡产生。
DOI：
10.1179/175889709x446516
发表时间：
2009
期刊：
Bubble science engineering and technology
影响因子：
--
作者：
Rapoport NY;Efros AL;Christensen DA;Kennedy AM;Nam KH
通讯作者：
Nam KH