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通过超声和微针滚轮增强利多卡因乳膏的透皮给药

Enhanced transdermal delivery of lidocaine cream via ultrasound and microneedle rollers.

作者信息

Sun Jiaxiao, Yang Yang, Zheng Juanjuan, Liang Hao, Yan Feng, Zhang Wensheng, Xie Wenqin

机构信息

Department of Anesthesiology, Quanzhou First Hospital, Fujian Medical University, Quanzhou, Fujian, China.

Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

出版信息

Front Bioeng Biotechnol. 2025 Jul 16;13:1612145. doi: 10.3389/fbioe.2025.1612145. eCollection 2025.

DOI:10.3389/fbioe.2025.1612145
PMID:40741537
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12307353/
Abstract

OBJECTIVE

The aim of this study is to determine the most effective physical parameters for optimizing the transdermal delivery of lidocaine cream.

METHODS

Preliminary experiments were conducted to optimize ultrasound settings while ensuring safety, guided by visual and histopathological evaluations following observations of skin burns in rats. assessments of lidocaine penetration into isolated porcine ear tissue were conducted using Franz diffusion cells and confocal laser scanning microscopy under different intervention conditions analysis involved measuring lidocaine concentrations in rat skin following treatments combining ultrasound and microneedle rollers. The anesthetic efficacy of these interventions was further assessed using the "rat tail-flick test."

RESULTS

Twelve non-invasive parameter configurations involving ultrasound and microneedle rollers were identified. The combination of ultrasound and microneedle rollers yielded superior results while the ultrasound-only groups demonstrated improved diffusion compared to the control. Notably, ultrasound applied at 260 kHz with a 90% duty cycle, in conjunction with microneedle rollers, achieved the highest diffusion rates, with cumulative lidocaine permeation at 15 min reaching 45.81 ± 4.19 μg/cm (vs. baseline 60 min value, p = 0.0017) and microneedle roller alone at 48.62 ± 6.73 μg/cm (p < 0.0001). Confocal laser scanning microscopy demonstrated minimal lidocaine penetration without interventions, whereas the combined ultrasound and microneedle approach resulted in significantly enhanced penetration, with visible fluorescence deep in the dermis within 5 min. findings corroborated these results, with the combined method facilitating the most rapid onset of anesthesia (mean onset time 28.75 ± 6.41 min, p < 0.05 vs control 67.50 ± 4.63 min) and improved transdermal delivery compared to other groups, achieving 100% anesthetic efficiency rate at 60 min vs. 25% in control.

CONCLUSION

Microneedle rollers demonstrate superior clinical efficacy over ultrasound, enabling rapid lidocaine delivery (15-min onset ; 32.5-min anesthesia ) and achieving 100% anesthetic efficiency for time-sensitive procedures-establishing a practical paradigm shift in transdermal local anesthesia.

摘要

目的

本研究旨在确定优化利多卡因乳膏透皮给药的最有效物理参数。

方法

在大鼠皮肤烧伤观察后的视觉和组织病理学评估指导下,进行初步实验以优化超声设置,同时确保安全性。在不同干预条件下,使用Franz扩散池和共聚焦激光扫描显微镜评估利多卡因对离体猪耳组织的渗透情况。分析包括测量联合超声和微针滚轮治疗后大鼠皮肤中的利多卡因浓度。使用“大鼠甩尾试验”进一步评估这些干预措施的麻醉效果。

结果

确定了12种涉及超声和微针滚轮的非侵入性参数配置。超声和微针滚轮的组合产生了更好的结果,而仅超声组与对照组相比显示出扩散改善。值得注意的是,以260kHz、90%占空比施加的超声与微针滚轮结合,实现了最高的扩散速率,15分钟时利多卡因的累积渗透量达到45.81±4.19μg/cm²(相对于基线60分钟值,p = 0.0017),单独微针滚轮为48.62±6.73μg/cm²(p < 0.0001)。共聚焦激光扫描显微镜显示在无干预情况下利多卡因渗透极少,而超声和微针联合方法导致渗透显著增强,5分钟内在真皮深层可见荧光。“大鼠甩尾试验”结果证实了这些结果,联合方法促进了麻醉的最快起效(平均起效时间28.75±6.41分钟,与对照组67.50±4.63分钟相比,p < 0.05),并且与其他组相比改善了透皮给药,60分钟时麻醉效率达到100%,而对照组为25%。

结论

微针滚轮在临床疗效上优于超声,能够实现利多卡因的快速给药(15分钟起效;32.5分钟麻醉),并在对时间敏感的手术中实现100%的麻醉效率,在经皮局部麻醉方面建立了切实可行的模式转变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21a8/12307353/3e8108bd9873/fbioe-13-1612145-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21a8/12307353/17a60bc1ab4b/fbioe-13-1612145-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21a8/12307353/bae8d1cee81c/fbioe-13-1612145-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21a8/12307353/6ec7082c4afe/fbioe-13-1612145-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21a8/12307353/d7b56311b762/fbioe-13-1612145-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21a8/12307353/fc0dcde8a80a/fbioe-13-1612145-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21a8/12307353/3e8108bd9873/fbioe-13-1612145-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21a8/12307353/17a60bc1ab4b/fbioe-13-1612145-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21a8/12307353/bae8d1cee81c/fbioe-13-1612145-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21a8/12307353/6ec7082c4afe/fbioe-13-1612145-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21a8/12307353/d7b56311b762/fbioe-13-1612145-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21a8/12307353/fc0dcde8a80a/fbioe-13-1612145-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21a8/12307353/3e8108bd9873/fbioe-13-1612145-g006.jpg

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