Enhanced intracellular delivery of a model drug using microbubbles produced by a microfluidic device.
Enhanced intracellular delivery of a model drug using microbubbles produced by a microfluidic device.
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DOI：
10.1016/j.ultrasmedbio.2013.01.023
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发表时间：
2013-07
影响因子：
2.9
通讯作者：
Hossack, John A.
中科院分区：
文献类型：
--
作者：
Dixon, Adam J.;Dhanaliwala, Ali H.;Chen, Johnny L.;Hossack, John A.
关键词：
血管内超声和微泡促进的局部药物输送到血管壁有望成为动脉粥样硬化的潜在治疗方法。微泡给药的常规方法导致从血流中快速清除和显著的药物损失。为了解决这些局限性，我们评估了药物递送是否可以实现与瞬时稳定的微泡实时和接近治疗部位。将大鼠主动脉平滑肌细胞置于设计用于模拟生理流动条件的流动室中。利用流动聚焦微流控装置（FFMD）在流动室内产生直径为8 μm的单分散微泡，并施加超声以增强替代药物（钙黄绿素）的摄取。声压高达300千帕和流量高达18毫升/秒进行了研究。FFMD产生的微泡用聚乙二醇-40硬脂酸酯壳稳定，并且具有全氟丁烷（PFB）或氮气核。气核组合物影响稳定性，PFB和氮气微泡的半衰期分别为40.7秒和18.2秒。与PFB微泡（200 kPa）相比，使用氮气微泡（100 kPa）在较低声压下观察到钙黄绿素摄取（p < 0.05，n ≥ 3）。此外，在所有流速下观察到递送，最大递送（> 70%的细胞）发生在9 mL/s的流速下。这些结果证明了瞬时稳定的微泡的潜力，实时和接近预期的治疗部位，以增强局部药物输送。
Focal drug delivery to a vessel wall facilitated by intravascular ultrasound and microbubbles holds promise as a potential therapy for atherosclerosis. Conventional methods of microbubble administration result in rapid clearance from the blood stream and significant drug loss. To address these limitations, we evaluated whether drug delivery could be achieved with transiently stable microbubbles produced in real-time and in close proximity to the therapeutic site. Rat aortic smooth muscle cells were placed in a flow chamber designed to simulate physiological flow conditions. A flow-focusing microfluidic device (FFMD) produced 8 μm diameter monodisperse microbubbles within the flow chamber, and ultrasound was applied to enhance uptake of a surrogate drug (calcein). Acoustic pressures up to 300 kPa and flow rates up to 18 mL/s were investigated. FFMD generated microbubbles were stabilized with a polyethylene glycol-40 stearate shell and had either a perfluorobutane (PFB) or nitrogen gas core. The gas core composition affected stability, with PFB and nitrogen microbubbles exhibiting half-lives of 40.7 and 18.2 seconds, respectively. Calcein uptake was observed at lower acoustic pressures with nitrogen microbubbles (100 kPa) than with PFB microbubbles (200 kPa) (p < 0.05, n ≥ 3). In addition, delivery was observed at all flow rates, with maximal delivery (> 70% of cells) occurring at a flow rate of 9 mL/s. These results demonstrate the potential of transiently stable microbubbles produced in real-time and in close proximity to the intended therapeutic site for enhancing localized drug delivery.
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DOI：
10.1109/tbme.2009.2034533
发表时间：
2010-01
期刊：
IEEE transactions on bio-medical engineering
影响因子：
--
作者：
Choi JJ;Feshitan JA;Baseri B;Wang S;Tung YS;Borden MA;Konofagou EE
通讯作者：
Konofagou EE
影响因子：
3.3
作者：
BUTLER, BD;HILLS, BA
通讯作者：
HILLS, BA
影响因子：
2.4
作者：
Guzmán, HR;Nguyen, DX;Prausnitz, MR
通讯作者：
Prausnitz, MR
影响因子：
2.4
作者：
JENSEN, JA
通讯作者：
JENSEN, JA
DOI：
10.1046/j.1540-8175.2002.00229.x
发表时间：
2002-04-01
影响因子：
1.5
作者：
de Jong, N;Bouakaz, A;Frinking, P
通讯作者：
Frinking, P