Banella Sabrina, Quarta Eride, Brandolini Martina, Grumiro Laura, Sambri Vittorio, Trevisi Giovanna, Bettini Ruggero, Colombo Paolo, Buttini Francesca, Sonvico Fabio, Caraua Georgeta, Rossi Alessandra, Colombo Gaia
Department of Life Sciences and Biotechnology, University of Ferrara, Via Fossato di Mortara 19, 44121, Ferrara, Italy.
Department of Diagnostics and Public Health, University of Verona, Piazzale L. Scuro 10, 37134, Verona, Italy.
Drug Deliv Transl Res. 2025 Jul 15. doi: 10.1007/s13346-025-01916-7.
During the COVID-19 pandemic, several compounds among which chloroquine diphosphate (CqP), have been repurposed as anti-SARS-CoV-2 drugs. Critically, studies were most often performed by systemic drug administration, whereas the early viral infection of human body appeared in the upper respiratory tract. This research addressed the delivery strategy for depositing a powder aerosol of CqP onto the upper airways by a nasal inhalation act. By formulating the drug as nasal microparticulate aerodynamic powder, the loco-regional application of particle aerosol concentrates the drug primarily on the upper airway epithelia where the virus replicates. Nasal microparticulate powders of CqP, with and without excipients, were engineered by spray drying, obtaining particle size, density and morphology suitable for aerosolization and deposition onto the upper respiratory tract. The powders were loaded into a pre-metered device for oral inhalation of dry powders that was innovatively actuated by a nasal sharp sniff. The generated nasal airflow, measured in healthy volunteers, enabled powder dose emission from the inhaler. Chloroquine diphosphate microparticles, deposited on rabbit nasal mucosa ex vivo, led in less than 45 min to CqP concentrations within the epithelial cells between 30-70 mM. The in vitro CqP concentrations inhibiting SARS-CoV-2 replication, were in the µM range. The virus inhibition studied in Vero E6 cells was further enhanced when the cells were pre-treated with the drug powder before infection. In conclusion, the simple nasal sniff of an antiviral aerodynamic powder could be active against airborne viral early infection, limiting the exposition of the whole body to undesired drug effects.
在新冠疫情期间，几种化合物，其中包括磷酸氯喹（CqP），已被重新用作抗SARS-CoV-2药物。关键的是，研究大多通过全身给药进行，而人体早期病毒感染出现在上呼吸道。本研究探讨了通过鼻吸动作将CqP粉末气雾剂沉积到上呼吸道的给药策略。通过将药物制成鼻用微粒气动粉末，局部应用颗粒气雾剂可使药物主要集中在病毒复制的上呼吸道上皮细胞上。通过喷雾干燥制备了含和不含辅料的CqP鼻用微粒粉末，获得了适合雾化并沉积在上呼吸道的粒径、密度和形态。这些粉末被装入一种用于口服吸入干粉的预定量装置中，该装置通过鼻快速吸气创新地驱动。在健康志愿者中测量的产生的鼻气流使粉末剂量从吸入器中喷出。磷酸氯喹微粒沉积在兔鼻黏膜离体标本上，在不到45分钟内使上皮细胞内的CqP浓度达到30 - 70 mM。体外抑制SARS-CoV-2复制的CqP浓度在微摩尔范围内。当Vero E6细胞在感染前用药物粉末预处理时，在该细胞中研究的病毒抑制作用进一步增强。总之，简单地鼻吸一种抗病毒气动粉末可能对空气传播的病毒早期感染有效，限制全身受到不良药物影响。
