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研究通过指甲的主动 Er:YLF 激光药物输送的两阶段方法和药物消光谱的激光诱导转变。

Investigation of the Dual-Stage Method of Active Er:YLF Laser Drug Delivery Through the Nail and Laser-Induced Transformations of the Drug Extinction Spectrum.

机构信息

Faculty of Laser Photonics and Optoelectronics, ITMO University, 49 Kronverksky Pr, St. Petersburg, 197101, Russia.

出版信息

Lasers Surg Med. 2021 Oct;53(8):1122-1131. doi: 10.1002/lsm.23379. Epub 2021 Jan 15.

Abstract

BACKGROUND AND OBJECTIVE

A novel dual-stage method for active laser drug delivery (DSLADD) in the treatment of nail diseases is being presented. This method includes sequentially performed microporation of the nail with submillisecond pulses of Er:YLF laser radiation through a layer of an aqueous solution of drug deposited on the nail surface (Stage 1) and exposure this layer to the same laser radiation to deliver drug under the nail plate (Stage 2). The delivery of methylene blue (MB) as one of the possible drugs in the treatment of nail diseases is investigated. The influence of the thickness of the MB layer, as well as the energy and number of applied laser pulses, on the rate of active laser delivery is discussed. To illustrate the possible effect of delivery on the drug delivered, special attention is paid to the deformation of the extinction spectrum of MB solution after laser irradiation.

STUDY DESIGN/MATERIALS AND METHODS: Diode-pumped Er:YLF laser was used for DSLADD. The process of DSLADD under the nail plate was investigated using digital video microscopy. For different values of the thickness of MB solution layer applied to the nail plate and the energy of laser pulses, the number of laser pulses required to create a single through a microchannel in the nail plate and the number of laser pulses required to deliver the solution to the ventral side of the nail plate after its microporation were registered. The mass and the dose of MB solution penetrated under the nail plate, and the rate of MB solution delivery through a single microchannel was determined. Investigation of the influence of Er:YLF laser radiation parameters on the extinction spectrum of the drug was performed using a fiber spectrometer. The extinction spectra of the 0.001% aqueous solution of MB were recorded before and after exposure to a different number of Er:YLF laser pulses with the energy of 1-4 mJ.

RESULTS

It was found that the minimum number of laser pulses required for active Er:YLF laser drug delivery under the nail corresponds to the MB layer thickness of 100 μm and the laser pulse energy of 4 mJ. It is shown that in this case, the rate of active laser delivery of MB solution reaches 0.26 ± 0.03 mg/pulse. The radiation of the Er:YLF laser affects the shape of the extinction spectrum of the aqueous solution of MВ, which is associated with the transition of the dye from the monomeric to dimeric state. Depending on the laser pulse energy, the fraction of a certain conformational state in the aqueous MB solution can decrease or increase, stimulating a possible change in its photodynamic and antiseptic activity.

CONCLUSION

For the first time, a novel DSLADD through the nail has been described and investigated in vitro. It was demonstrated that at Er:YLF laser pulse repetition rate of f = 30 Hz, microporation of the nail plate and drug delivery through a single microchannel will be about 1.5 s. Lasers Surg. Med. © 2021 Wiley Periodicals LLC.

摘要

背景与目的

本研究提出了一种新型的主动式激光药物输送(DSLADD)双阶段方法,用于治疗指甲疾病。该方法包括通过在指甲表面沉积一层药物的水溶液依次进行亚毫秒脉冲的 Er:YLF 激光微穿孔(第一阶段),以及将该层暴露于相同的激光辐射下以在指甲板下输送药物(第二阶段)。本研究以亚甲蓝(MB)作为治疗指甲疾病的潜在药物之一为例进行了研究。讨论了 MB 层厚度以及施加的激光脉冲能量和数量对主动激光输送速率的影响。为了说明输送对输送药物的可能影响,特别关注了激光辐照后 MB 溶液消光光谱的变形。

研究设计/材料和方法:使用二极管泵浦 Er:YLF 激光进行 DSLADD。使用数字视频显微镜研究指甲板下的 DSLADD 过程。对于施加在指甲板上的 MB 溶液层的不同厚度和激光脉冲能量,记录了在指甲板上创建单个微通道所需的激光脉冲数量,以及在微穿孔后将溶液输送到指甲板腹侧所需的激光脉冲数量。确定了穿透指甲板下的 MB 溶液的质量和剂量,以及通过单个微通道输送 MB 溶液的速率。使用光纤光谱仪研究了 Er:YLF 激光辐射参数对药物消光光谱的影响。记录了在不同数量的具有 1-4 mJ 能量的 Er:YLF 激光脉冲照射前后,0.001% MB 水溶液的消光光谱。

结果

发现主动 Er:YLF 激光药物输送到指甲下的最小激光脉冲数对应于 100 μm 的 MB 层厚度和 4 mJ 的激光脉冲能量。结果表明,在这种情况下,MB 溶液的主动激光输送速率达到 0.26±0.03 mg/脉冲。Er:YLF 激光的辐射会影响 MB 水溶液的消光光谱形状,这与染料从单体到二聚体状态的转变有关。根据激光脉冲能量,水溶液中 MB 的某种构象状态的比例可能会减少或增加,从而刺激其光动力和防腐活性的可能变化。

结论

本研究首次在体外描述并研究了一种新型的通过指甲的 DSLADD。结果表明,在 Er:YLF 激光脉冲重复率为 f=30 Hz 的情况下,指甲板的微穿孔和通过单个微通道的药物输送将耗时约 1.5 秒。

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