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Liposome leakage and increased cellular permeability induced by guanidine-based oligomers: effects of liposome composition on liposome leakage and human lung epithelial barrier permeability

Authors
Ha, YeonjeongKoo, YerimPark, Seon-KyungKim, Ga-EunOh, Han BinKim, Ha RyongKwon, Jung-Hwan
Issue Date
28-9월-2021
Publisher
ROYAL SOC CHEMISTRY
Citation
RSC ADVANCES, v.11, no.51, pp.32000 - 32011
Indexed
SCIE
SCOPUS
Journal Title
RSC ADVANCES
Volume
11
Number
51
Start Page
32000
End Page
32011
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/136296
DOI
10.1039/d1ra05478c
ISSN
2046-2069
Abstract
Over the decades, guanidine-based oligomer groups have been one of the most widely used antimicrobial agents. Reportedly, these cationic oligomers cause serious damage to microorganisms but have low toxicity to humans. However, public concerns regarding the guanidine group have rapidly grown after the fatal misuse of these oligomers as humidifier disinfectants, which resulted in thousands of fatalities in South Korea. Herein, we investigated liposome leakage and cellular permeability changes caused by polyhexamethylene guanidine (PHMG) and polyhexamethylene biguanide (PHMB), both representative guanidine-based oligomers. The leakage of zwitterionic liposomes, induced by cationic oligomers, was more extensive than that of negative liposomes, indicating that oligomer adsorption onto lipid head groups via electrostatic interaction cannot fully explain the induced lipid membrane damage. Furthermore, lipid packing parameters, including intrinsic curvature, cholesterol content, and lipid phases, affected liposome leakage, particularly for PHMG. Cellular permeability tests were performed using an A549 cell monolayer model and a respiratory 3D tissue model, revealing that PHMG and PHMB damaged cell membranes and reduced cell barrier function. Furthermore, liposome leakage induced by PHMG and PHMB was higher in human lung surfactant-mimicking liposomes than that observed in Escherichia coli-mimicking liposomes. These results indicated that human cells are susceptible to guanidine-based oligomers. Considering that the interaction of oligomers and cell membranes is a major mechanism of toxicity initiation, this study provides crucial insights into the action of these disinfectants on mammalian cells.
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Kwon, Jung Hwan
생명과학대학 (환경생태공학부)
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