Hydrogel-based drug carriers provide on-demand drug release via external stimuli. Ultrasound is a promising method because of the potential for remotely releasing the drug. However, intense ultrasound irradiation has been required in previous studies. This paper reports drug model release from hydrogel carriers encapsulating bubble vibration enhancers (BVEs) consisting of microbubbles coated with a lipid membrane. Vibration of BVEs induced by ultrasound stimulation promoted the release of drug models with ultrasound irradiation controlled to a biologically safe acoustic pressure based on spatial-peak temporal-average intensity (ISPTA). The release ratio increased significantly from 2.3 % without BVEs and ultrasound to 10.2 % with both. To evaluate the frequency response, the release ratio was measured at three different ultrasound frequencies (0.3, 1.8, and 2.5 MHz), showing increased efficiency as the frequency approached the resonance frequency of the BVEs. For in vivo applications, hydrogel microspherical carriers with BVEs achieved a 12 % release ratio. Poly-L-lysine coating successfully suppressed the drug release to 0.2 %. The carriers demonstrated repeated responsiveness when ultrasound was applied in three 5-minute intervals. The hydrogel carrier encapsulating BVEs we proposed is a promising in vivo device capable of releasing drugs on demand by ultrasound irradiation based on its high biosafety and acoustic responsiveness.

中文翻译：

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带有气泡振动增强剂的水凝胶载体，用于超声触发的药物释放


基于水凝胶的药物载体通过外部刺激提供按需药物释放。超声是一种很有前途的方法，因为它有可能远程释放药物。然而，在以前的研究中需要强烈的超声照射。本文报道了封装由脂质膜包被的微气泡组成的气泡增振剂 （BVE） 的水凝胶载体释放的药物模型。超声刺激诱导的 BVE 振动促进了药物模型的释放，超声照射控制在基于空间峰值时间平均强度 （ISPTA） 的生物安全声压。释放率从没有 BVE 和超声的 2.3% 显着增加到两者的 10.2%。为了评估频率响应，在三种不同的超声频率（0.3、1.8 和 2.5 MHz）下测量释放比，当频率接近 BVE 的共振频率时，效率增加。对于体内应用，带有 BVE 的水凝胶微球载体实现了 12% 的释放率。聚-L-赖氨酸包衣成功地将药物释放抑制到 0.2 %。当以 3 次 5 分钟的间隔进行超声检查时，携带者表现出重复的反应性。我们提出的封装 BVE 的水凝胶载体是一种很有前途的体内装置，能够基于其高生物安全性和声学响应性，通过超声照射按需释放药物。