Fractional laser-assisted drug delivery: Active filling of laser channels with pressure and vacuum alteration
Fractional laser-assisted drug delivery: Active filling of laser channels with pressure and vacuum alteration
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DOI：
10.1002/lsm.22374
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发表时间：
2016-02-01
影响因子：
2.4
通讯作者：
Haedersdal, Merete
中科院分区：
文献类型：
--
作者：
Erlendsson, Andres M.;Doukas, Apostolos G.;Haedersdal, Merete
背景与展望：作为皮肤给药的最重要技术之一，消融性分数激光（AFXL）正在迅速发展。虽然AFXL有效地改善了局部药物诱导的光化性角化病的清除率，但基底细胞癌（BCC）的治疗一直具有挑战性，这可能是由于深层皮肤中的药物摄取不足。本研究旨在研究通过改变压力、真空度和压力（PVP）来主动填充激光产生的通道的标准化方法，探讨其对（i）单个激光通道的相对填充;（ii）皮肤沉积和输送动力学;（iii）生物分布和扩散模式，通过数学模拟估计MethodsFranz扩散室（FCs）用于评估PVP技术，比较被动（AFXL）和主动（AFXL+PVP）通道填充。分数CO2激光产生浅表（225 μ m;17.5mJ/通道）和深（1200 μ m; 130.5mJ/通道）通道，PVP以1分钟压力（+1.0atm）、1分钟真空（-1.0atm）和1分钟压力（+1.0atm）的3分钟循环输送。用有色生物标志物液体（n=12个FC，n=588个通道）可视化激光通道的填充。核磁共振定量随时间（10分钟、1小时和4小时）局部应用的聚乙二醇（PEG 400）的皮内沉积，研究了PVP填充（n=36个FC）和未填充（n=30个FC）。二维数学模拟被用来模拟皮内生物分布和扩散的深度为1,000 μ m.ResultsActive填充与应用PVP的填充激光通道的数量增加。在1,000 μ m深度，一个PVP周期（AFXL+ PVP; P < 0.05）可使灌浆率从44%（AFXL）提高到94%（AFXL+PVP; P < 0.05）。
Background and ObjectiveAblative fractional laser (AFXL) is rapidly evolving as one of the foremost techniques for cutaneous drug delivery. While AFXL has effectively improved topical drug-induced clearance rates of actinic keratosis, treatment of basal cell carcinomas (BCCs) has been challenging, potentially due to insufficient drug uptake in deeper skin layers. This study sought to investigate a standardized method to actively fill laser-generated channels by altering pressure, vacuum, and pressure (PVP), enquiring its effect on (i) relative filling of individual laser channels; (ii) cutaneous deposition and delivery kinetics; (iii) biodistribution and diffusion pattern, estimated by mathematical simulation.MethodsFranz diffusion chambers (FCs) were used to evaluate the PVP-technique, comparing passive (AFXL) and active (AFXL+PVP) channel filling. A fractional CO2-laser generated superficial (225 mu m;17.5mJ/channel) and deep (1200 mu m; 130.5mJ/channel) channels, and PVP was delivered as a 3-minutes cycle of 1 minute pressure (+1.0atm), 1 minute vacuum (-1.0atm), and 1 minute pressure (+1.0atm). Filling of laser channels was visualized with a colored biomarker liquid (n=12 FCs, n=588 channels). Nuclear magnetic resonance quantified intracutaneous deposition of topically applied polyethylene glycol (PEG400) over time (10 minutes, 1 hour, and 4 hours), investigated with (n=36 FCs) and without (n=30 FCs) PVP-filling. Two-dimensional mathematical simulation was used to simulate intradermal biodistribution and diffusion at a depth of 1,000 mu m.ResultsActive filling with application of PVP increased the number of filled laser channels. At a depth of 1,000 mu m, filling increased from 44% (AFXL) to 94% with one PVP cycle (AFXL+PVP; P