He Qingwei, Lu Hong, Chen Yuying, Zeng Huiying, Hu Ping
Department of Burns & Plastic Surgery, Guangzhou Red Cross Hospital, Faculty of Medical Science, Jinan University, Guangzhou 510006, China; State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou 510006, China; College of Pharmacy, Jinan University, Guangzhou 510006, China.
State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou 510006, China; College of Pharmacy, Jinan University, Guangzhou 510006, China.
Acta Biomater. 2024 Dec;190:152-164. doi: 10.1016/j.actbio.2024.10.016. Epub 2024 Oct 12.
This study introduces a live imaging technique for real-time, non-invasive monitoring of drug release from long-acting microneedles using FRET (Fluorescence Resonance Energy Transfer). Employing Cy5.5 and Cy7 as FRET pairs and levonorgestrel as the model drug, we fabricated microneedles with varying PLGA molecular weights, demonstrating distinct release profiles. The FRET-PLGA-10-MN demonstrated a rapid drug release profile, reaching nearly complete release within a two-day period, while FRET-PLGA-30-MN showed a sustained release over four days. Sensitized Emission FRET (SE-FRET) optimized the imaging process, providing a robust correlation between FRET signals and drug absorption. This method surpasses traditional pharmacokinetic studies by offering a more efficient and comprehensive analysis of microneedle release dynamics in vivo, paving the way for enhanced long-acting microneedle design and therapeutic outcomes. STATEMENT OF SIGNIFICANCE: 1. FRET technology was applied to microneedle drug delivery system for the first time, which realized real-time, quantitative and non-invasive monitoring of drug release process. 2. The long-term microneedle technique was combined with sensitized emission method, and the FRET remaining ratio was innovatively used to investigate the FRET characteristics of microneedles, and the fluorescence ratio of FRET and donor double-channel was quantitatively calculated. 3. The correlation between visual fluorescence images of FRET effect and semi-quantitative calculation results based on fluorescence intensity and drug release in vivo with drug-loaded microneedles was analyzed.
本研究介绍了一种利用荧光共振能量转移（FRET）对长效微针药物释放进行实时、非侵入性监测的活体成像技术。以Cy5.5和Cy7作为FRET对，左炔诺孕酮作为模型药物，我们制备了具有不同聚乳酸-羟基乙酸共聚物（PLGA）分子量的微针，呈现出不同的释放曲线。FRET-PLGA-10-MN表现出快速的药物释放曲线，在两天内几乎达到完全释放，而FRET-PLGA-30-MN则显示出四天的持续释放。敏化发射FRET（SE-FRET）优化了成像过程，在FRET信号与药物吸收之间提供了有力的相关性。该方法通过对体内微针释放动力学进行更高效、全面的分析，超越了传统的药代动力学研究，为改进长效微针设计和治疗效果铺平了道路。重要性声明：1. FRET技术首次应用于微针给药系统，实现了对药物释放过程的实时、定量和非侵入性监测。2. 将长效微针技术与敏化发射方法相结合，创新性地利用FRET残留率研究微针的FRET特性，并定量计算FRET与供体双通道的荧光比率。3. 分析了FRET效应的视觉荧光图像与基于荧光强度和体内载药微针药物释放的半定量计算结果之间的相关性。
