Ultrasound and microbubbles (MBs) offer a noninvasive method of temporarily enhancing blood–brain barrier (BBB) permeability to therapeutics. To reduce off‐target effects, it is desirable to minimize the ultrasound pressures required. It has been shown that a new formulation of MBs containing lysolipids (Lyso‐MBs) can increase the cellular uptake of a model drug in vitro. The aim of this study is to investigate whether Lyso‐MBs can also enhance BBB permeability in vivo. Female BALB/c mice are injected with either Lyso‐MBs or control MBs and gadolinium‐DTPA (Gd‐DTPA) and exposed to ultrasound (500 kHz, 1 Hz pulse repetition frequency, 1 ms pulse length, peak‐negative pressures 160–480 kPa) for 2 min. BBB permeabilization is measured via magnetic resonance imaging (7.0 T) of Gd‐DTPA extravasation and subsequent histological examination of brain tissue to assess serum immunoglobulin G (IgG) extravasation (n = 8 per group). An approximately twofold enhancement in BBB permeability is produced by the Lyso‐MBs at the highest ultrasound pressure compared with the control. These findings indicate that modifying the composition of phospholipid‐shelled MBs has the potential to improve the efficiency of BBB opening, without increasing the ultrasound pressure amplitude required. This is particularly relevant for delivery of therapeutics deep within the brain.

中文翻译：

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包含溶血脂的微泡增强了超声介导的体内血脑屏障的破坏。

超声和微泡（MBs）提供了一种非侵入性方法，可暂时增强血脑屏障（BBB）对治疗的渗透性。为了减少脱靶效应，最好将所需的超声压力降至最低。已经表明，含有溶血脂（Lyso-MBs）的MB的新配方可以增加模型药物在体外的细胞吸收。这项研究的目的是研究Lyso-MBs是否还能在体内增强BBB的通透性。向雌性BALB / c小鼠注射Lyso-MB或对照MB和s DTPA（Gd-DTPA），并暴露于超声（500 kHz，1 Hz脉冲重复频率，1 ms脉冲长度，峰值负压160-480 kPa）2分钟。BBB通透性通过磁共振成像测量（7。每组n = 8）。与对照组相比，在最高超声压力下，Lyso-MBs可使BBB通透性提高大约两倍。这些发现表明，改变磷脂壳MB的组成具有提高BBB打开效率的潜力，而不会增加所需的超声压力幅度。这与大脑深处的治疗剂的输送特别相关。