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一种用于表征表皮伤口愈合并评估局部伤口愈合剂INM-755在健康志愿者中疗效的抽吸水疱模型。

A suction blister model to characterize epidermal wound healing and evaluate the efficacy of the topical wound healing agent INM-755 in healthy volunteers.

作者信息

Voorde Wouter Ten, Wind Selinde, Abdisalaam Ismahaan, Mancini Alexandra, Linders Feeke, Jansen Manon A A, Kolk Tessa Niemeyer-van der, Burggraaf Jacobus, Rissmann Robert

机构信息

Centre for Human Drug Research, Leiden, the Netherlands; Leiden University Medical Centre, Leiden, the Netherlands.

Centre for Human Drug Research, Leiden, the Netherlands; Department of Dermatology, Erasmus Medical Center, Rotterdam, the Netherlands.

出版信息

Eur J Pharm Sci. 2025 Jan 1;204:106867. doi: 10.1016/j.ejps.2024.106867. Epub 2024 Jul 29.

DOI:10.1016/j.ejps.2024.106867
PMID:39084539
Abstract

Non-healing wounds represent a substantial medical burden with few effective treatments available. To address this challenge, we developed a novel epidermal wound healing model using suction blisters in healthy volunteers. This model allowed for the comprehensive assessment of wound healing dynamics and the evaluation of INM-755, a topical cream containing cannabinol, as a potential therapeutic agent. Two clinical studies were conducted: an observational study and an interventional study. In both studies, healthy volunteers underwent a suction blister procedure on their lower back, creating open epidermal wounds. Wound healing parameters were assessed using advanced imaging systems. Skin barrier function and perfusion were evaluated through trans epidermal water loss (TEWL) and dynamic optical coherence tomography (D-OCT), respectively. The observational study demonstrated the successful and reproducible induction of blisters and the removal of epidermal sheet, enabling quantifiable measurements of wound healing parameters over time. Re-epithelialization was observed, revealing recovery of skin barrier function and perfusion. In the interventional study, differences of treatments over time were quantified using the above-described techniques. Despite differences from disease-specific blistering, our developed model provides a valuable platform for studying wound healing mechanisms and assessing novel therapeutic interventions. The sensitivity to treatment effects demonstrated in our study underscores the potential utility of this model in early-phase clinical drug development programs targeting wound healing disorders.

摘要

难愈合伤口带来了巨大的医疗负担,而有效的治疗方法却很少。为应对这一挑战,我们利用健康志愿者的抽吸性水疱开发了一种新型的表皮伤口愈合模型。该模型能够全面评估伤口愈合动态,并评估含有大麻酚的外用乳膏INM-755作为一种潜在治疗药物的效果。我们进行了两项临床研究:一项观察性研究和一项干预性研究。在这两项研究中,健康志愿者的下背部都接受了抽吸性水疱手术,形成开放性表皮伤口。使用先进的成像系统评估伤口愈合参数。分别通过经表皮水分流失(TEWL)和动态光学相干断层扫描(D-OCT)评估皮肤屏障功能和灌注情况。观察性研究表明水疱的诱导成功且可重复,表皮层被去除,从而能够对伤口愈合参数进行随时间的可量化测量。观察到了再上皮化现象,显示皮肤屏障功能和灌注得以恢复。在干预性研究中,使用上述技术对不同治疗随时间的差异进行了量化。尽管与特定疾病引起的水疱形成有所不同,但我们开发的模型为研究伤口愈合机制和评估新型治疗干预措施提供了一个有价值的平台。我们研究中所展示的对治疗效果的敏感性强调了该模型在针对伤口愈合障碍的早期临床药物开发项目中的潜在效用。

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