Ultrasound-triggered release from multilayered capsules
Ultrasound-triggered release from multilayered capsules
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DOI：
10.1002/smll.200600441
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发表时间：
2007-05-01
期刊：
影响因子：
13.3
通讯作者：
Sukhorukov, Gleb B.
中科院分区：
文献类型：
--
作者：
De Geest, Bruno G.;Skirtach, Andre G.;Sukhorukov, Gleb B.
对以所需方式释放其内容物的药物递送系统的需求不断增长，加强了对具有智能特性的“智能载体”的研究。[1-3]与更成熟的递送载体相比，例如聚合物胶束、[4]脂质体和小胶体颗粒[5]，聚合物电解质多层[6]胶囊[7, 8]是作为大分子药物递送系统具有很高潜力的新兴材料。[9-12]这些材料的主要优点微胶囊的特点是其负载能力以及通过选择胶囊的成分来精确调整其特性的可能性。大量的大分子治疗药物可以封装在这些胶囊内[13]，并且根据涂层材料的选择（即合成或生物），可以使胶囊不可降解或可降解。 [11]此外，它们的机械强度可以通过改变涂层的数量、[14]纳米粒子的含量、[15]或通过热处理来调整。[16, 17]一旦到达目标位点，最重要的是要有一种机制，使封装的物质从这些胶囊中释放出来。最近被证明可以通过激光照明实现外部触发释放。[18-20]该系统的原理是基于金属纳米粒子的加热，这会导致外壳渗透性的变化，甚至外壳完全破裂，最终导致封装材料的释放。[20]例如，这些激光敏感胶囊可以在细胞摄取后被激活[21]或用于透皮激活药物释放。在此，我们报告使用超声波来触发多层胶囊的释放。超声波已广泛应用于生物医学应用 [22]，用于改善药物吸收、抗炎治疗或成像。在传播时，超声波会经历粘性吸收、热吸收以及散射。 [23, 24] 在低频下，颗粒和介质之间的温差将处于平衡状态，而在高频下，只有一小部分表面会受到热波的影响。类似的频率依赖性适用于粘性损失，其中在低频下发生广泛的颗粒运动，而在高频下发生很少的运动。图 1 示意性地显示了胶囊的制造以及超声波对其完整性的影响。当胶囊受到超声波作用时，由于连续流体层之间产生剪切力，胶囊壁发生形态变化，导致胶囊膜破裂并释放封装物质。
The growing need for drug-delivery systems that release their contents in a desired fashion has intensified research for “smart carriers” with intelligent properties.[1–3] Compared to more established delivery vehicles, such as polymeric micelles,[4] liposomes, and small colloidal particles,[5] polymeric polyelectrolyte multilayered [6] capsules [7, 8] are emerging materials with high potential as macromolecular drug-delivery systems.[9–12] The major advantages of these microcapsules are their loading capacity and the possibility to precisely tailor their properties by choosing the components of the capsules. Considerable amounts of macromolecular therapeutics can be encapsulated inside these capsules [13] and, depending on the choice of coating material (ie, synthetic or biological), one can render capsules nondegradable or degradable.[11] Also, their mechanical strength can be tailored by varying the number of coating layers,[14] inclusion of nanoparticles,[15] or by thermal treatment.[16, 17] Once their target site is reached, it is of utmost importance to have a mechanism that causes release of encapsulated species from these capsules. Externally triggered release has recently been shown to be possible by laser-light illumination.[18–20] The principle of this system is based on heating of metal nanoparticles, which causes changes in permeability of the outer shell and even total disruption of the shell, finally resulting in the release of the encapsulated material.[20] These laser-light-sensitive capsules could, for example, be activated after cellular uptake [21] or be used for transdermal activated-drug release.Herein, we report the use of ultrasound to trigger release from multilayered capsules. Ultrasound has been used widely in biomedical applications [22] for improving drug uptake, anti-inflammatory treatment, or imaging. Upon propagation, an ultrasound wave undergoes both viscous and thermal absorption as well as scattering.[23, 24] At low frequency the temperature difference between the particle and the medium will be in equilibrium, whereas at high frequency only a small portion of the surface will be affected by thermal waves. Similar frequency dependence is applicable to viscous losses, wherein extensive particle motion occurs at low frequency while little movement takes place at high frequencies. Figure 1 shows schematically the fabrication of the capsules and the effect of ultrasound on their integrity. When the capsules are subjected to ultrasound, a morphological change of the capsule wall occurs due to the creation of shear forces between the successive fluid layers, which results in the disruption of the capsule membrane and release of encapsulated species.