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制定一种复合鼻腔喷雾剂,可增强 SARS-CoV-2 的表面覆盖率并预防其感染。

Formulation of a Composite Nasal Spray Enabling Enhanced Surface Coverage and Prophylaxis of SARS-COV-2.

机构信息

Healthcare Technology Institute, School of Chemical Engineering, University of Birmingham, Birmingham, B15 2TT, UK.

Institute of Immunology and Immunotherapy, School of Medicine and Dentistry, University of Birmingham, Birmingham, B15 2GW, UK.

出版信息

Adv Mater. 2021 Jul;33(26):e2008304. doi: 10.1002/adma.202008304. Epub 2021 May 31.

Abstract

Airborne pathogens pose high risks in terms of both contraction and transmission within the respiratory pathways, particularly the nasal region. However, there is little in the way of adequate intervention that can protect an individual or prevent further spread. This study reports on a nasal formulation with the capacity to combat such challenges, focusing on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Formulation of a polysaccharide-based spray, known for its mucoadhesive properties, is undertaken and it is characterized for its mechanical, spray distribution, and antiviral properties. The ability to engineer key mechanical characteristics such as dynamic yield stresses and high coverage is shown, through systematic understanding of the composite mixture containing both gellan and λ-carrageenan. Furthermore, the spray systems demonstrate highly potent capacities to prevent SARS-CoV-2 infection in Vero cells, resulting in complete inhibition when either treating, the cells, or the virus, prior to challenging for infection. From this data, a mechanism for both prophylaxis and prevention is proposed; where entrapment within a polymeric coating sterically blocks virus uptake into the cells, inactivating the virus, and allowing clearance within the viscous medium. As such, a fully preventative spray is formulated, targeted at protecting the lining of the upper respiratory pathways against SARS-CoV-2.

摘要

空气中的病原体通过呼吸道,尤其是鼻腔,在传播和感染方面带来了高风险。然而,目前几乎没有有效的干预手段来保护个人或阻止其进一步传播。本研究报告了一种针对此类挑战的鼻腔制剂,重点研究了严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)。研究采用了一种多糖喷雾制剂,该制剂具有粘弹性,其机械性能、喷雾分布和抗病毒特性都得到了研究。通过对包含结冷胶和 λ-卡拉胶的复合混合物的系统理解,展示了对关键机械特性(如动态屈服应力和高覆盖度)进行工程设计的能力。该喷雾系统在预防 Vero 细胞感染 SARS-CoV-2 方面表现出很强的能力,当在病毒感染前对细胞或病毒进行治疗或预防时,可完全抑制病毒感染。基于这些数据,提出了一种预防和治疗的机制;聚合物涂层的截留作用会阻碍病毒进入细胞,从而使病毒失活,并在粘性介质中清除。因此,开发了一种针对 SARS-CoV-2 的预防性喷雾,旨在保护上呼吸道免受感染。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/088b/11469187/d7eea6952ec6/ADMA-33-2008304-g005.jpg

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