Ultrasound Nanobubble Coupling Agent for Effective Noninvasive Deep-Layer Drug Delivery

作者全名："Han, Xiaoyu; Wang, Fan; Shen, Jieliang; Chen, Shuyu; Xiao, Pengcheng; Zhu, Ying; Yi, Weiwei; Zhao, Zhengyu; Cai, Zhengwei; Cui, Wenguo; Bai, Dingqun"

作者地址："[Han, Xiaoyu; Chen, Shuyu; Xiao, Pengcheng; Zhu, Ying; Yi, Weiwei; Bai, Dingqun] Chongqing Med Univ, Affiliated Hosp 1, Dept Rehabil Med, Chongqing 400010, Peoples R China; [Wang, Fan; Zhao, Zhengyu; Cai, Zhengwei; Cui, Wenguo] Shanghai Jiao Tong Univ, Shanghai Inst Traumatol & Orthopaed, Shanghai Key Lab Prevent & Treatment Bone & Joint, Ruijin Hosp,Dept Orthopaed,Sch Med, 197 Ruijin 2nd Rd, Shanghai 200025, Peoples R China; [Shen, Jieliang] Chongqing Med Univ, Bishan Hosp, Bishan Hosp Chongqing, Dept Rehabil Med, Chongqing 402760, Peoples R China; [Bai, Dingqun] Chongqing Med Univ, State Key Lab Ultrasound Med & Engn, Chongqing 400016, Peoples R China"

通信作者："Bai, DQ (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Rehabil Med, Chongqing 400010, Peoples R China.; Cai, ZW; Cui, WG (通讯作者)，Shanghai Jiao Tong Univ, Shanghai Inst Traumatol & Orthopaed, Shanghai Key Lab Prevent & Treatment Bone & Joint, Ruijin Hosp,Dept Orthopaed,Sch Med, 197 Ruijin 2nd Rd, Shanghai 200025, Peoples R China.; Bai, DQ (通讯作者)，Chongqing Med Univ, State Key Lab Ultrasound Med & Engn, Chongqing 400016, Peoples R China."

来源：ADVANCED MATERIALS

ESI学科分类：MATERIALS SCIENCE

WOS号：WOS:001111784700001

JCR分区：Q1

影响因子：27.4

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：Achilles tendon adhesions; coupling agent; deep-layer drug delivery; noninvasive; ultrasound

摘要："Conventional coupling agents (such as polyvinylpyrrolidone, methylcellulose, and polyurethane) are unable to efficiently transport drugs through the skin's dual barriers (the epidermal cuticle barrier and the basement membrane barrier between the epidermis and dermis) when exposed to ultrasound, hindering deep and noninvasive transdermal drug delivery. In this study, nanobubbles prepared by the double emulsification method and aminated hyaluronic acid are crosslinked with aldehyde-based hyaluronic acid by dynamic covalent bonding through the Schiff base reaction to produce an innovative ultrasound-nanobubble coupling agent. By amplifying the cavitation effect of ultrasound, drugs can be efficiently transferred through the double barrier of the skin and delivered to deep layers. In an in vitro model of isolated porcine skin, this agent achieves an effective penetration depth of 728 mu m with the parameters of ultrasound set at 2 W, 650 kHz, and 50% duty cycle for 20 min. Consequently, drugs can be efficiently delivered to deeper layers noninvasively. In summary, this ultrasound nanobubble coupling agent efficiently achieves deep-layer drug delivery by amplifying the ultrasonic cavitation effect and penetrating the double barriers, heralding a new era for noninvasive drug delivery platforms and disease treatment. Ultrasound nanobubbles and aminated hyaluronic acid prepared by the double emulsification method are crosslinked with aldehyde-based hyaluronic acid via dynamic covalent bonds through the Schiff base reaction to produce an innovative ultrasound-nanobubble coupling agent. By amplifying the cavitation effect of ultrasound, drugs can be efficiently transferred through the double barrier of the skin and delivered to deep layers.image"

基金机构："The National Natural Science Foundation of Chongqing [2020YFA0908200]; National Key Research and Development Program of China [82172533, 82002402, 32101104]; National Natural Science Foundation of China [CSTB2022NSCQ-MSX0792]; National Natural Science Foundation of Chongqing [CXQT21018]; Chongqing Municipal Education Commission, Innovative Research Group of Universities in Chongqing [2020KFA3019]; State Key Laboratory of Ultrasound Engineering in Medicine and Engineering [202140127]; Shanghai Municipal Health Planning Commission [W0076]; Program for Youth Innovation in Future Medicine, Chongqing Medical University"

基金资助正文："X.H., F.W., and J.S. contributed equally to this work. This work was supported in part by the National Key Research and Development Program of China (Nos. 2020YFA0908200), National Natural Science Foundation of China (Nos. 82172533, 82002402, and 32101104), The National Natural Science Foundation of Chongqing (No. CSTB2022NSCQ-MSX0792),Chongqing Municipal Education Commission, Innovative Research Group of Universities in Chongqing (No. CXQT21018), State Key Laboratory of Ultrasound Engineering in Medicine and Engineering (No. 2020KFA3019), Shanghai Municipal Health Planning Commission (No. 202140127), Program for Youth Innovation in Future Medicine, Chongqing Medical University (No. W0076)"