Ceriotti Laura, Buratti Paolo, Corazziari Enrico Stefano, Meloni Marisa
In vitro Innovation Center, VitroScreen srl, Milan, Italy.
Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano (Milan), Italy.
Med Devices (Auckl). 2022 May 18;15:143-152. doi: 10.2147/MDER.S363616. eCollection 2022.
A novel experimental design based on a human-reconstructed oesophageal epithelium (HO2E) model has been applied to quantitively assess the properties of a set of liquid formulations, Device A (Gerdoff Protection), Device B (Esoxx One), and Device C (Marial gel) developed to form a temporary physical barrier on the oesophageal epithelium and modify epithelial permeability so to protect the oesophageal mucosa from refluxate components.
The formulations were applied to a prewetted HO2E model for 15 min. Then, a 0.5% caffeine solution was applied, and its penetration kinetics was assessed at 1 h and 2 h in acidic environments (pH= 3.3) to mirror exposure of the oesophageal mucosa to acidic reflux in GORD patients. Caffeine permeated into the basolateral compartment (evaluated by HPLC-UV) and Lucifer yellow (LY) permeability were quantified 15 min after application of the caffeine in acidic environments.
At the 15 min timepoint, Device A reduced caffeine permeation by 77.2% and LY flux by 30.4% compared to the untreated control and with a faster mode of action than that of the other liquid formulations. Transepithelial caffeine flux was reduced, albeit with different timing and efficiency, by all three compounds up to the end of the 2 hour experiment. At 1 h, Device A reduced the caffeine flux by 79.2%; Device B, by 67.2%; and Device C, by 37%.
These results confirm the ability of the medical devices tested to interact with the oesophageal epithelium and create a temporary physical protective film for up to 2 hours after their application. The results underline differences in the mechanism of action of the three medical devices, with Device A performing faster than the other formulations. The overall results support the relevance of the reconstructed mucosal model to investigate oesophageal epithelium-product interactions and precisely differentiate liquid formulation performance.
一种基于人重建食管上皮（HO2E）模型的新型实验设计已被用于定量评估一组液体制剂的性能，这些制剂包括装置A（Gerdoff保护剂）、装置B（Esoxx One）和装置C（Marial凝胶），它们旨在在食管上皮上形成临时物理屏障并改变上皮通透性，从而保护食管黏膜免受反流物成分的侵害。
将这些制剂应用于预先湿润的HO2E模型15分钟。然后，应用0.5%的咖啡因溶液，并在酸性环境（pH = 3.3）中1小时和2小时评估其渗透动力学，以模拟胃食管反流病（GORD）患者食管黏膜暴露于酸性反流物的情况。在酸性环境中应用咖啡因15分钟后，通过高效液相色谱-紫外检测法（HPLC-UV）评估咖啡因渗透到基底外侧隔室的情况，并对荧光素黄（LY）的通透性进行定量分析。
在15分钟时间点，与未处理的对照组相比，装置A使咖啡因的渗透率降低了77.2%，使LY通量降低了30.4%，并且其作用模式比其他液体制剂更快。在2小时实验结束时，所有三种化合物均降低了跨上皮咖啡因通量，尽管时间和效率不同。在1小时时，装置A使咖啡因通量降低了79.2%；装置B降低了67.2%；装置C降低了37%。
这些结果证实了所测试的医疗器械与食管上皮相互作用并在应用后长达2小时形成临时物理保护膜的能力。结果强调了这三种医疗器械作用机制的差异，装置A的作用速度比其他制剂更快。总体结果支持了重建黏膜模型在研究食管上皮与产品相互作用以及精确区分液体制剂性能方面的相关性。
