Journal Article Epublish
PubMed: 40447732 DOI: 10.1038/s41598-025-04673-2
Exploring intracellular anti-mycobacterium activity of lactoferricin-loaded niosomes: proteomics insights into Immunomodulation.
Sci Rep 15(1):19029
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
Affiliations
- Division of Clinical Microbiology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 50200, Thailand.
- Infectious Diseases Research Unit (IDRU), Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 50200, Thailand.
- Office of Research Administration, Chiang Mai University, Chiang Mai, 50200, Thailand.
- Department of Chemistry, Faculty of Sciences, Chiang Mai University, Chiang Mai, 50200, Thailand.
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, 50200, Thailand.
- Functional Proteomics Technology Laboratory, National Center for Genetic Engineering and Biotechnology, National Science and Technology for Development Agency, Pathum Thani, 12120, Thailand.
- Office of Disease Prevention and Control 1, Chiang Mai, 50200, Thailand.
- Division of Clinical Microbiology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 50200, Thailand.
- Infectious Diseases Research Unit (IDRU), Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 50200, Thailand.
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.
MeSH
Complement C6, Immunomodulation, Mycobacterium, Proteomics, Therapeutics
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