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Storage stability of lysostaphin solution and its pulmonary delivery

Zeng, P; Zhang, P; Chan, HW; Chow, SF; Lam, JKW; Ip, M; Leung, SSY; (2024) Storage stability of lysostaphin solution and its pulmonary delivery. Drug Delivery and Translational Research 10.1007/s13346-024-01518-9. (In press). Green open access

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Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) has become a leading causative pathogen of nosocomial pneumonia with an alarming in-hospital mortality rate of 30%. Last resort antibiotic, vancomycin, has been increasingly used to treat MRSA infections, but the rapid emergence of vancomycin-resistant strains urges the development of alternative treatment strategies against MRSA-associated pneumonia. The bacteriolytic enzyme, lysostaphin, targeting the cell wall peptidoglycan of S. aureus, has been considered as a promising alternative for MRSA infections. Its proteinaceous nature is likely benefit from direct delivery to the lungs, but the challenges for successful pulmonary delivery of lysostaphin lying on a suitable inhalation device and a formulation with sufficient storage stability. In this study, the applicability of a vibrating mesh nebulizer (Aerogen Solo®) and a soft mist inhaler (Respimat®) was investigated. Both devices were capable of aerosolizing lysostaphin solution into inhalable droplets and caused minimum antibacterial activity loss. In addition, lysostaphin stabilized with phosphate-buffered saline and 0.1% Tween 80 was proved to have acceptable stability for at least 12 months when stored at 4 °C. These promising data encourage further clinical development of lysostaphin for management of MRSA-associated lung infections. Graphical abstract: [Figure not available: see fulltext.] Lysostaphin had insignificant activity loss after aerosol generation by a vibrating mesh nebulizer and a soft mist inhaler.Most of the lysostaphin aerosols generated by the vibrating mesh nebulizer and soft mist inhaler are inhalable.The vibrating mesh nebulizer and soft mist inhaler are suitable device for pulmonary delivery of lysostaphin.

Type: Article
Title: Storage stability of lysostaphin solution and its pulmonary delivery
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/s13346-024-01518-9
Publisher version: https://doi.org/10.1007/s13346-024-01518-9
Language: English
Additional information: © 2024 Springer Nature. This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).
Keywords: Inhalation therapy, Bacterial lung infections, Multidrug-resistant bacteria, MRSA, Bacteriolytic enzyme Peptidoglycan
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics
URI: https://discovery.ucl.ac.uk/id/eprint/10186118
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