Almazi Juhura G, Silva Dina M, Trotta Valentina, Fiore Walter, Ong Hui X, Traini Daniela
Respiratory Technology, Woolcock Institute of Medical Research, Sydney, NSW 2037, Australia.
Ab Initio Pharma Pte Ltd., 63-73 Missenden Road, Camperdown, NSW 2050, Australia.
Pharmaceutics. 2022 Jun 22;14(7):1323. doi: 10.3390/pharmaceutics14071323.
The exposure of lung epithelium to environmental hazards is linked to several chronic respiratory diseases. We assessed the ability of an inhaled dry powder (DPI) medical device product (PolmonYDEFENCE/DYFESA, SOFAR SpA, Trezzano Rosa, Italy), using a formulation of sodium hyaluronate (Na-Hya) as the key ingredient as a defensive barrier to protect the upper respiratory tract. Specifically, it was evaluated if the presence of the barrier formed by sodium hyaluronate present on the cells, reducing direct contact of the urban dust (UD) with the surface of cells can protect them in an indirect manner by the inflammatory and oxidative process started in the presence of the UD. Cytotoxicity and the protection capability against the oxidative stress of the product were tested in vitro using Calu-3 cells exposure to UD as a trigger for oxidative stress. Inflammation and wound healing were assessed using an air-liquid interface (ALI) culture model of the Calu-3 cells. Deposition studies of the formulation were conducted using a modified Anderson cascade impactor (ACI) and the monodose PillHaler dry powder inhaler (DPI) device, Na-Hya was detected and quantified using high-performance-liquid-chromatography (HPLC). Solubilised PolmonYDEFENCE/DYFESA gives protection against oxidative stress in Calu-3 cells in the short term (2 h) without any cytotoxic effects. ALI culture experiments, testing the barrier-forming (non-solubilised) capabilities of PolmonYDEFENCE/DYFESA, showed that the barrier layer reduced inflammation triggered by UD and the time for wound closure compared to Na-Hya alone. Deposition experiments using the ACI and the PillHaler DPI device showed that the majority of the product was deposited in the upper part of the respiratory tract. Finally, the protective effect of the product was efficacious for up to 24 h without affecting mucus production. We demonstrated the potential of PolmonYDEFENCE/DYFESA as a preventative barrier against UD, which may aid in protecting the upper respiratory tract against environmental hazards and help with chronic respiratory diseases.
肺上皮细胞暴露于环境危害因素与多种慢性呼吸道疾病有关。我们评估了一种吸入式干粉（DPI）医疗器械产品（PolmonYDEFENCE/DYFESA，SOFAR SpA，意大利特雷扎诺罗萨）的能力，该产品使用透明质酸钠（Na-Hya）制剂作为关键成分，作为一种防御屏障来保护上呼吸道。具体而言，评估了细胞上由透明质酸钠形成的屏障的存在，减少城市灰尘（UD）与细胞表面的直接接触，是否能通过在UD存在时启动的炎症和氧化过程以间接方式保护细胞。使用Calu-3细胞暴露于UD作为氧化应激触发因素，在体外测试了该产品的细胞毒性和抗氧化应激保护能力。使用Calu-3细胞的气液界面（ALI）培养模型评估炎症和伤口愈合情况。使用改良的安德森级联撞击器（ACI）和单剂量PillHaler干粉吸入器（DPI）装置进行制剂的沉积研究，使用高效液相色谱（HPLC）检测和定量Na-Hya。溶解的PolmonYDEFENCE/DYFESA在短期内（2小时）对Calu-3细胞的氧化应激具有保护作用，且无任何细胞毒性作用。ALI培养实验测试了PolmonYDEFENCE/DYFESA的屏障形成（未溶解）能力，结果表明与单独的Na-Hya相比，屏障层减少了UD引发的炎症和伤口闭合时间。使用ACI和PillHaler DPI装置的沉积实验表明，大部分产品沉积在上呼吸道上部。最后，该产品的保护作用在长达24小时内有效，且不影响黏液分泌。我们证明了PolmonYDEFENCE/DYFESA作为针对UD的预防性屏障的潜力，这可能有助于保护上呼吸道免受环境危害并有助于治疗慢性呼吸道疾病。
