Preclinical assessment of an antibiotic-free cationic surfactant-based cellulose hydrogel for sexually and perinatally transmitted infections

Rita D.A. Calado; Bárbara B. Mendes; João Conniot; João M.J.M. Ravasco; Daniel Sobral; Carolina Ferreira; Rita Ferreira; João Carlos Rodrigues; Daniela Santos; Sílvia Duarte; Luís Vieira; Ângela S. Inácio; Henrique Carrêlo; Winchil L.C. Vaz; João Paulo Gomes; Alexandra Nunes; João Conde; Otilia V. Vieira

doi:10.1016/j.matt.2024.04.002

Preclinical assessment of an antibiotic-free cationic surfactant-based cellulose hydrogel for sexually and perinatally transmitted infections

Rita D.A. Calado, Bárbara B. Mendes, João Conniot, João M.J.M. Ravasco, Daniel Sobral, Carolina Ferreira, Rita Ferreira, João Carlos Rodrigues, Daniela Santos, Sílvia Duarte, Luís Vieira, Ângela S. Inácio, Henrique Carrêlo, Winchil L.C. Vaz, João Paulo Gomes, Alexandra Nunes, João Conde, Otilia V. Vieira

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

Abstract

Sexually transmitted infections and urogenital-perinatal infections are significant health challenges owing to their asymptomatic nature, multidrug-resistant pathogens, and lack of effective vaccines. Surfactants are under investigation as potential antimicrobial agents and alternatives to traditional antibiotics. Here, we discovered that N-dodecylpyridinium bromide (C₁₂PB), a cationic quaternary ammonium surfactant, has very low potential to induce antimicrobial resistance with no antibiotic cross-resistance or inflammation in vitro. Therefore, we developed a preclinical antibiotic-free cationic surfactant-based cellulose hydrogel for treating sexually transmitted infections. The C₁₂PB-hydrogels provided sustained surfactant release, enhancing their biocompatibility and antibacterial activity without inflammation or epithelial disruption of the vaginal tract. In a preclinical model of Neisseria gonorrhoeae infection, a single application of the C₁₂PB-hydrogel showed a 2- to 3-fold reduction in infection. This lays the foundation for the future development of C₁₂PB-hydrogels for sexually transmitted infections, demonstrating potent antibacterial activity and minimal risk of antimicrobial resistance or inflammation.

Original language	English
Pages (from-to)	2205-2235
Number of pages	31
Journal	Matter
Volume	7
Issue number	6
DOIs	https://doi.org/10.1016/j.matt.2024.04.002
Publication status	Published - 1 Jun 2024

Bibliographical note

Publisher Copyright:
© 2024 Elsevier Inc.

Funding

This work was financially supported by the Foundation for Science and Technology of the Portuguese Ministry of Science and Higher Education ( PTDC/BIA-MIC/31561/2017 ) through national funds and co-funded by FEDER under the PT2020 Partnership. B.B.M., J. Conniot, and J. Conde acknowledge the European Research Council \u2019s Starting Grant ( ERC-StG-2019-848325 ). R.D.A.C. was supported by the FCT project PTDC/BIA-MIC/31561/2017 . O.V.V. was supported by CEEC INST ref. CEECINST/00102/2018/CP1567/CT0020 (DOI: 10.54499/CEECINST/00102/2018/CP1567/CT0020). This work is also a result of the GenomePT project (POCI-01-0145-FEDER-022184), supported by the COMPETE 2020\u2013Operational Programme for Competitiveness and Internationalization (POCI), Lisboa Portugal Regional Operational Programme (Lisboa2020), Algarve Portugal Regional Operational Programme (CRESC Algarve2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and by Funda\u00E7\u00E3o para a Ci\u00EAncia e a Tecnologia (FCT). We thank Prof. Teresa Cidade for assistance with rheological studies. We thank the Histopathology Unit at Gulbenkian Science Institute for quantitative pathology evaluation and the Histological Facility at Nova Medical School for technical assistance with sample preparation.

Funders	Funder number
Fundação para a Ciência e a Tecnologia
European Regional Development Fund
Ministério da Ciência, Tecnologia e Ensino Superior	PTDC/BIA-MIC/31561/2017
European Research Council	ERC-StG-2019-848325
CEEC INST	CEECINST/00102/2018/CP1567/CT0020

Keywords

MAP 6: Development
Neisseria gonorrhoeae
Streptococcus agalactiae
antibiotic-free
antimicrobial resistance
hydrogel
perinatal transmitted infections
sexually transmitted infections
surfactant

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10.1016/j.matt.2024.04.002

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Calado, R. D. A., Mendes, B. B., Conniot, J., Ravasco, J. M. J. M., Sobral, D., Ferreira, C., Ferreira, R., Rodrigues, J. C., Santos, D., Duarte, S., Vieira, L., Inácio, Â. S., Carrêlo, H., Vaz, W. L. C., Gomes, J. P., Nunes, A., Conde, J., & Vieira, O. V. (2024). Preclinical assessment of an antibiotic-free cationic surfactant-based cellulose hydrogel for sexually and perinatally transmitted infections. Matter, 7(6), 2205-2235. https://doi.org/10.1016/j.matt.2024.04.002

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title = "Preclinical assessment of an antibiotic-free cationic surfactant-based cellulose hydrogel for sexually and perinatally transmitted infections",

abstract = "Sexually transmitted infections and urogenital-perinatal infections are significant health challenges owing to their asymptomatic nature, multidrug-resistant pathogens, and lack of effective vaccines. Surfactants are under investigation as potential antimicrobial agents and alternatives to traditional antibiotics. Here, we discovered that N-dodecylpyridinium bromide (C12PB), a cationic quaternary ammonium surfactant, has very low potential to induce antimicrobial resistance with no antibiotic cross-resistance or inflammation in vitro. Therefore, we developed a preclinical antibiotic-free cationic surfactant-based cellulose hydrogel for treating sexually transmitted infections. The C12PB-hydrogels provided sustained surfactant release, enhancing their biocompatibility and antibacterial activity without inflammation or epithelial disruption of the vaginal tract. In a preclinical model of Neisseria gonorrhoeae infection, a single application of the C12PB-hydrogel showed a 2- to 3-fold reduction in infection. This lays the foundation for the future development of C12PB-hydrogels for sexually transmitted infections, demonstrating potent antibacterial activity and minimal risk of antimicrobial resistance or inflammation.",

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doi = "10.1016/j.matt.2024.04.002",

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Calado, RDA, Mendes, BB, Conniot, J, Ravasco, JMJM, Sobral, D, Ferreira, C, Ferreira, R, Rodrigues, JC, Santos, D, Duarte, S, Vieira, L, Inácio, ÂS, Carrêlo, H, Vaz, WLC, Gomes, JP , Nunes, A, Conde, J & Vieira, OV 2024, 'Preclinical assessment of an antibiotic-free cationic surfactant-based cellulose hydrogel for sexually and perinatally transmitted infections', Matter, vol. 7, no. 6, pp. 2205-2235. https://doi.org/10.1016/j.matt.2024.04.002

TY - JOUR

T1 - Preclinical assessment of an antibiotic-free cationic surfactant-based cellulose hydrogel for sexually and perinatally transmitted infections

AU - Calado, Rita D.A.

AU - Mendes, Bárbara B.

AU - Conniot, João

AU - Ravasco, João M.J.M.

AU - Sobral, Daniel

AU - Ferreira, Carolina

AU - Ferreira, Rita

AU - Rodrigues, João Carlos

AU - Santos, Daniela

AU - Duarte, Sílvia

AU - Vieira, Luís

AU - Inácio, Ângela S.

AU - Carrêlo, Henrique

AU - Vaz, Winchil L.C.

AU - Gomes, João Paulo

AU - Nunes, Alexandra

AU - Conde, João

AU - Vieira, Otilia V.

PY - 2024/6/1

Y1 - 2024/6/1

N2 - Sexually transmitted infections and urogenital-perinatal infections are significant health challenges owing to their asymptomatic nature, multidrug-resistant pathogens, and lack of effective vaccines. Surfactants are under investigation as potential antimicrobial agents and alternatives to traditional antibiotics. Here, we discovered that N-dodecylpyridinium bromide (C12PB), a cationic quaternary ammonium surfactant, has very low potential to induce antimicrobial resistance with no antibiotic cross-resistance or inflammation in vitro. Therefore, we developed a preclinical antibiotic-free cationic surfactant-based cellulose hydrogel for treating sexually transmitted infections. The C12PB-hydrogels provided sustained surfactant release, enhancing their biocompatibility and antibacterial activity without inflammation or epithelial disruption of the vaginal tract. In a preclinical model of Neisseria gonorrhoeae infection, a single application of the C12PB-hydrogel showed a 2- to 3-fold reduction in infection. This lays the foundation for the future development of C12PB-hydrogels for sexually transmitted infections, demonstrating potent antibacterial activity and minimal risk of antimicrobial resistance or inflammation.

AB - Sexually transmitted infections and urogenital-perinatal infections are significant health challenges owing to their asymptomatic nature, multidrug-resistant pathogens, and lack of effective vaccines. Surfactants are under investigation as potential antimicrobial agents and alternatives to traditional antibiotics. Here, we discovered that N-dodecylpyridinium bromide (C12PB), a cationic quaternary ammonium surfactant, has very low potential to induce antimicrobial resistance with no antibiotic cross-resistance or inflammation in vitro. Therefore, we developed a preclinical antibiotic-free cationic surfactant-based cellulose hydrogel for treating sexually transmitted infections. The C12PB-hydrogels provided sustained surfactant release, enhancing their biocompatibility and antibacterial activity without inflammation or epithelial disruption of the vaginal tract. In a preclinical model of Neisseria gonorrhoeae infection, a single application of the C12PB-hydrogel showed a 2- to 3-fold reduction in infection. This lays the foundation for the future development of C12PB-hydrogels for sexually transmitted infections, demonstrating potent antibacterial activity and minimal risk of antimicrobial resistance or inflammation.

KW - MAP 6: Development

KW - Neisseria gonorrhoeae

KW - Streptococcus agalactiae

KW - antibiotic-free

KW - antimicrobial resistance

KW - hydrogel

KW - perinatal transmitted infections

KW - sexually transmitted infections

KW - surfactant

UR - http://www.scopus.com/inward/record.url?scp=85192466096&partnerID=8YFLogxK

U2 - 10.1016/j.matt.2024.04.002

DO - 10.1016/j.matt.2024.04.002

M3 - Article

AN - SCOPUS:85192466096

SN - 2590-2393

VL - 7

SP - 2205

EP - 2235

JO - Matter

JF - Matter

IS - 6

ER -

Preclinical assessment of an antibiotic-free cationic surfactant-based cellulose hydrogel for sexually and perinatally transmitted infections

Abstract

Bibliographical note

Funding

Keywords

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