A Single Short 'Tone Burst' Results in Optimal Drug Delivery to Tumours Using Ultrasound-Triggered Therapeutic Microbubbles.
A Single Short 'Tone Burst' Results in Optimal Drug Delivery to Tumours Using Ultrasound-Triggered Therapeutic Microbubbles.
复制标题
DOI：
10.3390/pharmaceutics14030622
复制
发表时间：
2022-03-11
期刊：
影响因子：
5.4
通讯作者：
Coletta PL
中科院分区：
文献类型：
--
作者：
Ingram N;McVeigh LE;Abou-Saleh RH;Batchelor DVB;Loadman PM;McLaughlan JR;Markham AF;Evans SD;Coletta PL
先进的药物输送系统，如超声介导的药物输送，显示出很大的希望，提高治疗指数。通过改变超声参数来改善递送已经在体外进行了大量研究，但在体内研究相对较少。在这里，使用相同的治疗微泡和肿瘤类型来确定改变超声参数是否可以改善药物输送。脂质体装载有SN 38并通过抗生物素蛋白：生物素连接与微泡连接。通过加入抗血管内皮生长因子受体2抗体将整个结构靶向肿瘤血管系统。在将超声触发器应用于肿瘤区域后，在SW 480异种移植物中定量肿瘤药物递送和代谢。将触发持续时间从5s增加到2min或增加5s触发的数量并没有改善药物递送，也没有改变为旨在刺激更大比例的微泡群体的啁啾触发，尽管这确实表明短音调触发导致更多的游离SN 38释放。在体内检查超声触发以改善药物递送是合理的，因为有多种机制在起作用，可能不允许直接从体外结果转换。在这种情况下，短脉冲声为肿瘤药物输送提供了最佳的超声参数。
Advanced drug delivery systems, such as ultrasound-mediated drug delivery, show great promise for increasing the therapeutic index. Improvements in delivery by altering the ultrasound parameters have been studied heavily in vitro but relatively little in vivo. Here, the same therapeutic microbubble and tumour type are used to determine whether altering ultrasound parameters can improve drug delivery. Liposomes were loaded with SN38 and attached via avidin: biotin linkages to microbubbles. The whole structure was targeted to the tumour vasculature by the addition of anti-vascular endothelial growth factor receptor 2 antibodies. Tumour drug delivery and metabolism were quantified in SW480 xenografts after application of an ultrasound trigger to the tumour region. Increasing the trigger duration from 5 s to 2 min or increasing the number of 5 s triggers did not improve drug delivery, nor did changing to a chirp trigger designed to stimulate a greater proportion of the microbubble population, although this did show that the short tone trigger resulted in greater release of free SN38. Examination of ultrasound triggers in vivo to improve drug delivery is justified as there are multiple mechanisms at play that may not allow direct translation from in vitro findings. In this setting, a short tone burst gives the best ultrasound parameters for tumoural drug delivery.
登录
查看更多内容
影响因子：
4.6
作者：
Damioli V;Salvadori A;Beretta GP;Ravelli C;Mitola S
通讯作者：
Mitola S
影响因子：
5.4
作者：
Bulbake U;Doppalapudi S;Kommineni N;Khan W
通讯作者：
Khan W
影响因子：
14
作者：
Fan, Ching-Hsiang;Ting, Chien-Yu;Yeh, Chih-Kuang
通讯作者：
Yeh, Chih-Kuang
DOI：
10.1073/pnas.1606915113
发表时间：
2016-09-06
影响因子：
11.1
作者：
Helfield, Brandon;Chen, Xucai;Villanueva, Flordeliza S.
通讯作者：
Villanueva, Flordeliza S.
影响因子：
3.5
作者：
Kamimura HA;Wang S;Wu SY;Karakatsani ME;Acosta C;Carneiro AA;Konofagou EE
通讯作者：
Konofagou EE