Can bacteriophage endolysins be nebulised for inhalation delivery against Streptococcus pneumoniae?

Can bacteriophage endolysins be nebulised for inhalation delivery against Streptococcus pneumoniae?

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Item Type: Article
Status: Published
Official URL:
Journal or Publication Title: International Journal of Pharmaceutics
Volume: 591
Page Range: p. 119982
Date: 2020
Divisions: Tuberculosis
Depositing User: General Admin
Identification Number: 10.1016/j.ijpharm.2020.119982
ISSN: 03785173
Date Deposited: 29 Mar 2021 05:55

Endolysins are bacteriophage-derived protein molecules highly effective for bacterial killing. Cpl-1 and ClyJ-3 are native and chimeric endolysins, respectively, having antimicrobial activity against Streptococcus pneumoniae which causes lung infections. We conducted the first feasibility study on nebulisation of Cpl-1 and ClyJ-3, with a focus on the antimicrobial activity, structural changes of the proteins and aerosol performance. Bacterial colony counts, live cell imaging and Fourier-transform infrared(FTIR) spectroscopy were used to evaluate the proteins before and after jet or vibrating mesh nebulisation. These nebulised aerosols were inhalable with a volume median size of 3.8-4.2 µm (span 1.1-2.3) measured by laser diffraction. How-ever, neb-u-li-sa-tion caused al-most com-plete loss in bioac-tiv-ity of ClyJ-3, which were corroborated with the live cell imaging observation and protein structural damage with a large intensity reduction in the amide absorption bands between 1300 and 1700 cm-1. In contrast, the bactericidal activity of Cpl-1 showed no significant difference (p ≥ 0.05) before and after mesh nebulisation with 4.9 and 4.6-log10 bacterial count reduction, respectively. However, jet nebulisation reduced the bioactivity of Cpl-1 and the effect was time-dependent showing 1.7, 1.0-log10 bacterial count reduction at 7 and 14 min with complete loss of antimicrobial activity at 21 min after nebulisation, respectively. The results were consistent with time-dependent changes in live cell images and FTIR amide band changes at 1655, 1640, 1632 and 1548 cm-1. In conclusion, it is feasible to nebulise endolysins for inhalation delivery but it depends on both the protein and the nebuliser, with the mesh nebuliser being the preferred choice.

Keywords: Bacteriophage endolysins; Endolysin delivery; FTIR; Nebulisation; Nebuliser; Respiratory infection; Streptococcus pneumoniae.

Copyright © 2020 Elsevier B.V. All rights reserved.

Wang, Yuncheng
Khanal, Dipesh
Chang, Rachel Yoon Kyung
Shang, Xiaoran
Yang, Hang
Britton, Warwick J.
Nelson, Daniel
Chan, Hak-Kim
Last Modified: 29 Mar 2021 05:55

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