Exploring intracellular anti-mycobacterium activity of lactoferricin-loaded niosomes: proteomics insights into Immunomodulation

Abstract Tuberculosis (TB) treatment faces significant challenges due to prolonged therapy and drug resistance, necessitating innovative anti-TB strategies. Thus, developing an innovative platform with effective anti-TB activity would offer more advantages. In this study, the pH-sensitive niosomal f...

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Main Authors: Sirikwan Sangboonruang, Natthawat Semakul, Worrapan Poomanee, Thasang Thavanapong, Sittiruk Roytrakul, Sawanya Charoenlappanit, Siriwan Thaisakun, Jiaranai Khantipongse, Nathiprada Netirat, Apiwadee Tongsong, Usanee Wattananandkul, Sorasak Intorasoot, Ponrut Phunpae, Khajornsak Tragoolpua
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-04673-2
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author Sirikwan Sangboonruang
Natthawat Semakul
Worrapan Poomanee
Thasang Thavanapong
Sittiruk Roytrakul
Sawanya Charoenlappanit
Siriwan Thaisakun
Jiaranai Khantipongse
Nathiprada Netirat
Apiwadee Tongsong
Usanee Wattananandkul
Sorasak Intorasoot
Ponrut Phunpae
Khajornsak Tragoolpua
author_facet Sirikwan Sangboonruang
Natthawat Semakul
Worrapan Poomanee
Thasang Thavanapong
Sittiruk Roytrakul
Sawanya Charoenlappanit
Siriwan Thaisakun
Jiaranai Khantipongse
Nathiprada Netirat
Apiwadee Tongsong
Usanee Wattananandkul
Sorasak Intorasoot
Ponrut Phunpae
Khajornsak Tragoolpua
author_sort Sirikwan Sangboonruang
collection DOAJ
description Abstract Tuberculosis (TB) treatment faces significant challenges due to prolonged therapy and drug resistance, necessitating innovative anti-TB strategies. Thus, developing an innovative platform with effective anti-TB activity would offer more advantages. In this study, the pH-sensitive niosomal formulation of lactoferricin (Lfcin-Nio) was fabricated using a microfluidic system. The optimization of Lfcin-Nio formulation was statistically carried out based on the Central Composite Design (CCD). The desirable properties of Lfcin-Nio were achieved with a small particle size (171.68 ± 0.97 nm), a narrow polydispersity index; PDI (0.24 ± 0.002), an acceptable zeta potential; ZP (− 69.86 ± 0.64 mV), and high entrapment efficiency; %EE (75.59 ± 2.78%) with a prediction error of less than 5%. Lfcin-Nio demonstrated low cytotoxicity and stability for 28 days at room temperature and 4 °C. Lfcin-Nio also had a release profile in response to acidic pH, with approximately 50%, 70%, and 80% cumulative release at pH 7.4, 6.5, and 5.5, respectively, within the first 6 h. Notably, Lfcin-Nio exhibited enhanced anti-mycobacterial activity against both extracellular and intracellular Mycobacterium tuberculosis (Mtb), requiring a lower concentration for intracellular Mtb attenuation. Proteomic analysis revealed that Lfcin-Nio modulated immune response-related proteins, including complement C6 activation and suppression of inflammatory mediators. These findings suggest that Lfcin-Nio represents a promising anti-TB agent and further applies as a potential advancement in TB therapy.
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spelling doaj-art-04b8b60a1f5a4c2792544d2975e187ae2025-08-20T02:03:35ZengNature PortfolioScientific Reports2045-23222025-05-0115111710.1038/s41598-025-04673-2Exploring intracellular anti-mycobacterium activity of lactoferricin-loaded niosomes: proteomics insights into ImmunomodulationSirikwan Sangboonruang0Natthawat Semakul1Worrapan Poomanee2Thasang Thavanapong3Sittiruk Roytrakul4Sawanya Charoenlappanit5Siriwan Thaisakun6Jiaranai Khantipongse7Nathiprada Netirat8Apiwadee Tongsong9Usanee Wattananandkul10Sorasak Intorasoot11Ponrut Phunpae12Khajornsak Tragoolpua13Division of Clinical Microbiology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai UniversityDepartment of Chemistry, Faculty of Sciences, Chiang Mai UniversityDepartment of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai UniversityDepartment of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai UniversityFunctional Proteomics Technology Laboratory, National Center for Genetic Engineering and Biotechnology, National Science and Technology for Development AgencyFunctional Proteomics Technology Laboratory, National Center for Genetic Engineering and Biotechnology, National Science and Technology for Development AgencyFunctional Proteomics Technology Laboratory, National Center for Genetic Engineering and Biotechnology, National Science and Technology for Development AgencyOffice of Disease Prevention and Control 1Office of Disease Prevention and Control 1Office of Disease Prevention and Control 1Division of Clinical Microbiology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai UniversityDivision of Clinical Microbiology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai UniversityDivision of Clinical Microbiology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai UniversityDivision of Clinical Microbiology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai UniversityAbstract Tuberculosis (TB) treatment faces significant challenges due to prolonged therapy and drug resistance, necessitating innovative anti-TB strategies. Thus, developing an innovative platform with effective anti-TB activity would offer more advantages. In this study, the pH-sensitive niosomal formulation of lactoferricin (Lfcin-Nio) was fabricated using a microfluidic system. The optimization of Lfcin-Nio formulation was statistically carried out based on the Central Composite Design (CCD). The desirable properties of Lfcin-Nio were achieved with a small particle size (171.68 ± 0.97 nm), a narrow polydispersity index; PDI (0.24 ± 0.002), an acceptable zeta potential; ZP (− 69.86 ± 0.64 mV), and high entrapment efficiency; %EE (75.59 ± 2.78%) with a prediction error of less than 5%. Lfcin-Nio demonstrated low cytotoxicity and stability for 28 days at room temperature and 4 °C. Lfcin-Nio also had a release profile in response to acidic pH, with approximately 50%, 70%, and 80% cumulative release at pH 7.4, 6.5, and 5.5, respectively, within the first 6 h. Notably, Lfcin-Nio exhibited enhanced anti-mycobacterial activity against both extracellular and intracellular Mycobacterium tuberculosis (Mtb), requiring a lower concentration for intracellular Mtb attenuation. Proteomic analysis revealed that Lfcin-Nio modulated immune response-related proteins, including complement C6 activation and suppression of inflammatory mediators. These findings suggest that Lfcin-Nio represents a promising anti-TB agent and further applies as a potential advancement in TB therapy.https://doi.org/10.1038/s41598-025-04673-2TuberculosisLactoferricinNiosomeAnti-mycobacterium activityProteomicsImmune responses
spellingShingle Sirikwan Sangboonruang
Natthawat Semakul
Worrapan Poomanee
Thasang Thavanapong
Sittiruk Roytrakul
Sawanya Charoenlappanit
Siriwan Thaisakun
Jiaranai Khantipongse
Nathiprada Netirat
Apiwadee Tongsong
Usanee Wattananandkul
Sorasak Intorasoot
Ponrut Phunpae
Khajornsak Tragoolpua
Exploring intracellular anti-mycobacterium activity of lactoferricin-loaded niosomes: proteomics insights into Immunomodulation
Scientific Reports
Tuberculosis
Lactoferricin
Niosome
Anti-mycobacterium activity
Proteomics
Immune responses
title Exploring intracellular anti-mycobacterium activity of lactoferricin-loaded niosomes: proteomics insights into Immunomodulation
title_full Exploring intracellular anti-mycobacterium activity of lactoferricin-loaded niosomes: proteomics insights into Immunomodulation
title_fullStr Exploring intracellular anti-mycobacterium activity of lactoferricin-loaded niosomes: proteomics insights into Immunomodulation
title_full_unstemmed Exploring intracellular anti-mycobacterium activity of lactoferricin-loaded niosomes: proteomics insights into Immunomodulation
title_short Exploring intracellular anti-mycobacterium activity of lactoferricin-loaded niosomes: proteomics insights into Immunomodulation
title_sort exploring intracellular anti mycobacterium activity of lactoferricin loaded niosomes proteomics insights into immunomodulation
topic Tuberculosis
Lactoferricin
Niosome
Anti-mycobacterium activity
Proteomics
Immune responses
url https://doi.org/10.1038/s41598-025-04673-2
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