文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期,新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

通过双靶向粉末制剂中和 SARS-CoV-2 的单克隆抗体。

Neutralisation of SARS-CoV-2 by monoclonal antibody through dual targeting powder formulation.

机构信息

Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong Special Administrative Region; Department of Pharmaceutics, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, WC1N 1AX, UK.

Department of Microbiology, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong Special Administrative Region.

出版信息

J Control Release. 2023 Jun;358:128-141. doi: 10.1016/j.jconrel.2023.04.029. Epub 2023 Apr 30.


DOI:10.1016/j.jconrel.2023.04.029
PMID:37084889
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10148961/
Abstract

Neutralising monoclonal antibody (mAb) is an important weapon in our arsenal for combating respiratory viral infections. However, the effectiveness of neutralising mAb has been impeded by the rapid emergence of mutant variants. Early administration of broad-spectrum mAb with improved delivery efficiency can potentially enhance efficacy and patient outcomes. WKS13 is a humanised mAb which was previously demonstrated to exhibit broad-spectrum activity against SARS-CoV-2 variants. In this study, a dual targeting formulation strategy was designed to deliver WKS13 to both the nasal cavity and lower airways, the two critical sites of infection caused by SARS-CoV-2. Dry powders of WKS13 were first prepared by spray drying, with cyclodextrin used as stabiliser excipient. Two-fluid nozzle (TFN) was used to produce particles below 5 μm for lung deposition (C-TFN formulation) and ultrasonic nozzle (USN) was used to produce particles above 10 μm for nasal deposition (C-USN formulation). Gel electrophoresis and size exclusion chromatography studies showed that the structural integrity of mAb was successfully preserved with no sign of aggregation after spray drying. To achieve dual targeting property, C-TFN and C-USN were mixed at various ratios. The aerosolisation property of the mixed formulations dispersed from a nasal powder device was examined using a Next Generation Impactor (NGI) coupled with a glass expansion chamber. When the ratio of C-TFN in the mixed formulation increased, the fraction of particles deposited in the lung increased proportionally while the fraction of particles deposited in the nasal cavity decreased correspondingly. A customisable aerosol deposition profile could therefore be achieved by manipulating the mixing ratio between C-TFN and C-USN. Dual administration of C-TFN and C-USN powders to the lung and nasal cavity of hamsters, respectively, was effective in offering prophylactic protection against SARS-CoV-2 Delta variant. Viral loads in both the lung tissues and nasal wash were significantly reduced, and the efficacy was comparable to systemic administration of unformulated WKS13. Overall, dual targeting powder formulation of neutralising mAb is a promising approach for prophylaxis of respiratory viral infections. The ease and non-invasive administration of dual targeting nasal powder may facilitate the widespread distribution of neutralising mAb during the early stage of unpredictable outbreaks.

摘要

中和单克隆抗体 (mAb) 是我们对抗呼吸道病毒感染的重要武器。然而,中和 mAb 的有效性受到突变变体快速出现的阻碍。早期使用具有改善递送效率的广谱 mAb 进行给药,可能会提高疗效并改善患者结局。WKS13 是一种人源化 mAb,先前已被证明对 SARS-CoV-2 变体具有广谱活性。在这项研究中,设计了一种双重靶向制剂策略,将 WKS13 递送到鼻腔和下呼吸道,这是 SARS-CoV-2 感染的两个关键部位。首先通过喷雾干燥制备 WKS13 的干粉,其中使用环糊精作为稳定剂赋形剂。使用双流喷嘴 (TFN) 产生用于肺部沉积的小于 5μm 的颗粒(C-TFN 制剂),并使用超声喷嘴 (USN) 产生用于鼻腔沉积的大于 10μm 的颗粒(C-USN 制剂)。凝胶电泳和尺寸排阻色谱研究表明,mAb 的结构完整性在喷雾干燥后成功得到保留,没有聚集的迹象。为了实现双重靶向特性,将 C-TFN 和 C-USN 以各种比例混合。使用下一代撞击器 (NGI) 结合玻璃扩展室,检查来自鼻粉装置的混合制剂的气溶胶化特性。当混合制剂中 C-TFN 的比例增加时,肺部沉积的颗粒分数相应地成比例增加,而鼻腔沉积的颗粒分数相应地减少。因此,通过操纵 C-TFN 和 C-USN 之间的混合比例,可以实现可定制的气溶胶沉积分布。分别将 C-TFN 和 C-USN 粉末双重给药到仓鼠的肺部和鼻腔中,对 SARS-CoV-2 Delta 变体有效提供预防保护。肺部组织和鼻腔冲洗液中的病毒载量均显著降低,疗效与未配制的 WKS13 的全身给药相当。总体而言,中和 mAb 的双重靶向粉末制剂是预防呼吸道病毒感染的一种很有前途的方法。双重靶向鼻粉的简便性和非侵入性给药方式可能会促进中和 mAb 在不可预测的暴发早期阶段的广泛分发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/766b/10148961/a89556e2505b/gr7_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/766b/10148961/1e0e54429fa1/ga1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/766b/10148961/78552633827f/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/766b/10148961/cbca18c66075/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/766b/10148961/143684f46a26/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/766b/10148961/e530812574eb/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/766b/10148961/b91c4c235f9e/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/766b/10148961/d6e67f0155da/gr6_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/766b/10148961/a89556e2505b/gr7_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/766b/10148961/1e0e54429fa1/ga1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/766b/10148961/78552633827f/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/766b/10148961/cbca18c66075/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/766b/10148961/143684f46a26/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/766b/10148961/e530812574eb/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/766b/10148961/b91c4c235f9e/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/766b/10148961/d6e67f0155da/gr6_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/766b/10148961/a89556e2505b/gr7_lrg.jpg

相似文献

[1]
Neutralisation of SARS-CoV-2 by monoclonal antibody through dual targeting powder formulation.

J Control Release. 2023-6

[2]
Dual targeting powder formulation of antiviral agent for customizable nasal and lung deposition profile through single intranasal administration.

Int J Pharm. 2022-5-10

[3]
Intranasal delivery of thin-film freeze-dried monoclonal antibodies using a powder nasal spray system.

Int J Pharm. 2024-3-25

[4]
Enhanced powder dispersion of dual-excipient spray-dried powder formulations of a monoclonal antibody and its fragment for local treatment of severe asthma.

Int J Pharm. 2023-9-25

[5]
Inhalable dry powders of a monoclonal antibody against SARS-CoV-2 virus made by thin-film freeze-drying.

Int J Pharm. 2024-9-5

[6]
Spray-Dried and Spray-Freeze-Dried Powder Formulations of an Anti-Interleukin-4Rα Antibody for Pulmonary Delivery.

Pharm Res. 2022-9

[7]
A dry powder formulation for peripheral lung delivery and absorption of an anti-SARS-CoV-2 ACE2 decoy polypeptide.

Eur J Pharm Sci. 2023-12-1

[8]
Preparation and Characterization of Inhalable Ivermectin Powders as a Potential COVID-19 Therapy.

J Aerosol Med Pulm Drug Deliv. 2022-10

[9]
Dry powders for inhalation containing monoclonal antibodies made by thin-film freeze-drying.

Int J Pharm. 2022-4-25

[10]
Spray drying siRNA-lipid nanoparticles for dry powder pulmonary delivery.

J Control Release. 2022-11

引用本文的文献

[1]
Cyclodextrin-Based Nanotransporters as a Versatile Tool to Manage Oxidative Stress-Induced Lung Diseases.

Antioxidants (Basel). 2025-8-17

[2]
Characterization of Spray-Dried Powders Using a Coated Alberta Idealized Nasal Inlet.

J Aerosol Med Pulm Drug Deliv. 2025-2

[3]
Dry powder formulations of hyperimmune serum.

Drug Deliv Transl Res. 2025-4

[4]
Respiratory delivery of passive immunotherapies for SARS-CoV-2 prophylaxis and therapy.

Hum Vaccin Immunother. 2023-8

本文引用的文献

[1]
Inhalable neutralizing antibodies - promising approach to combating respiratory viral infections.

Trends Pharmacol Sci. 2023-2

[2]
Real-World Evidence of Neutralizing Monoclonal Antibodies for Preventing Hospitalization and Mortality in COVID-19 Outpatients.

Chest. 2023-5

[3]
Comparative analysis of SARS-CoV-2 Omicron BA.2.12.1 and BA.5.2 variants.

J Med Virol. 2023-1

[4]
Unbiased approach to identify and assess efficacy of human SARS-CoV-2 neutralizing antibodies.

Sci Rep. 2022-9-15

[5]
A potent neutralizing antibody provides protection against SARS-CoV-2 Omicron and Delta variants via nasal delivery.

Signal Transduct Target Ther. 2022-8-30

[6]
Inhalable microparticle platform based on a novel shell-forming lipid excipient and its feasibility for respirable delivery of biologics.

Eur J Pharm Biopharm. 2022-8

[7]
Prescription of Anti-Spike Monoclonal Antibodies in COVID-19 Patients with Resistant SARS-CoV-2 Variants in Italy.

Pathogens. 2022-7-22

[8]
Spray-Dried and Spray-Freeze-Dried Powder Formulations of an Anti-Interleukin-4Rα Antibody for Pulmonary Delivery.

Pharm Res. 2022-9

[9]
Antibody evasion by SARS-CoV-2 Omicron subvariants BA.2.12.1, BA.4 and BA.5.

Nature. 2022-8

[10]
Contribution of low population immunity to the severe Omicron BA.2 outbreak in Hong Kong.

Nat Commun. 2022-6-24

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索