Visually controlled pulsatile release of insulin from chitosan poly-acrylic acid nanobubbles triggered by focused ultrasound

作者全名："Yi, Xiyuan; Luo, Yong; Zhou, Qi; Wang, Jun; Yang, Zengtao"

作者地址："[Yi, Xiyuan; Luo, Yong; Yang, Zengtao] Chongqing Med Univ, Coll Biomed Engn, State Key Lab Ultrasound Med & Engn, Chongqing 400016, Peoples R China; [Yi, Xiyuan; Zhou, Qi; Wang, Jun] Chongqing Univ, Fuling Hosp, Chongqing 408099, Peoples R China"

通信作者："Yang, ZT (通讯作者)，Chongqing Med Univ, Coll Biomed Engn, State Key Lab Ultrasound Med & Engn, Chongqing 400016, Peoples R China."

来源：INTERNATIONAL JOURNAL OF PHARMACEUTICS

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001048838800001

JCR分区：Q1

影响因子：5.3

年份：2023

卷号：643

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Pulsatile release; Visually controlled release; Ultrasound triggered drug delivery; Insulin; Poly-acrylic acid nanobubbles

摘要："Insulin therapy is the most effective way to control the blood glucose value of diabetic patients. The most effective administration route for insulin is subcutaneous injection because bioavailability for non-injection administration is low and unstable. However, patients often need a multiple daily insulin injection regimen to control basal and postprandial blood glucose, which causes various complications. Controlled pulsatile drug release technology using ultrasound as an external stimulus source is a very promising method to avoid multiple injections of insulin. However, most of the drug-loaded microbubbles used for ultrasound-mediated treatment have a short half-life, which limits their use in controlled pulsatile drug release. More importantly, how to control insulin release is still a challenge. In this paper, chitosan poly-acrylic acid nanobubbles as drug carriers of insulin were prepared to achieve a visually controlled pulsatile release of insulin triggered by focused ultrasound. The experimental results in vivo demonstrated that nanobubbles were stable enough to achieve long-term visualization for 7 days after intramuscular injection in rats. Under the guidance of ultrasound imaging, it is visible to find the position and observe the gray values change of nanobubbles. Thus, when triggered by focused ultrasound, the amount of insulin could be accurately pulsatile released from nanobubbles. In vivo experiments in rats showed that the visually controlled pulsatile release of insulin could be achieved for a long time, up to 3 consecutive days. The blood glucose level could be repeatedly reduced by focused ultrasound irradiation with just one injection. Our research provided a promising way for visually controlled pulsatile release of insulin, which would significantly reduce the injection frequency of insulin."

基金机构："Program for Youth Innovation in Future Medicine, Chongqing Medical University [W0015, cqmudstd202222]; Chongqing Natural Science Foundation Post- doctoral Fund [cstc2021jcyj-bshX0169]"

基金资助正文："Acknowledgements We are grateful for the financial support from Program for Youth Innovation in Future Medicine, Chongqing Medical University, Project No. W0015, Chongqing postgraduate mentor team under Grant cqmudstd202222, and Chongqing Natural Science Foundation Post- doctoral Fund, Project No. cstc2021jcyj-bshX0169."