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image of Thymol-Loaded Zinc Ferrite Nanoparticles: A Novel Carrier for 
Enhanced Antimicrobial and Antibiofilm Activity against M. smegmatis through ROS-Mediated Mechanism

Abstract

Introduction/Objective

Tuberculosis (TB) remains a persistent global health challenge, with an increasing incidence of cases and limitations in current treatment strategies. Traditional therapy involves long drug treatments that can cause side effects and lead to drug-resistant strains, making treatment less effective. This study aimed to explore the therapeutic potential of a novel nanoparticle-based delivery system for Thymol (THY), a natural antibacterial bioactive molecule, to combat , a model organism for .

Methods

A nanoparticle-based delivery system was developed using biocompatible Thymol-conjugated Chitosan Zinc Ferrite Nanoparticles (THY-CH-ZnFe2O4 NPs). The nanoconjugates were characterized for their morphological and chemical properties.

Results

The characterization of synthesised nanoparticles showed THY-CH-ZnFe2O4 NPs to exhibit enhanced biocompatibility and antibacterial activity against compared to THY alone. The nanoconjugates induced Reactive Oxygen Species (ROS)-mediated damage to the bacterial cell membrane, effectively inhibiting bacterial replication, dormancy, and biofilm formation. Additionally, the nanoconjugates demonstrated low cytotoxicity towards the human kidney cell line.

Conclusion

The study's findings highlighted a new direction for developing nanoparticle-based antimycobacterial agents with a wide application in treating TB and other bacterial diseases. The THY-CH-ZnFe2O4 NPs show promise as a safe and effective therapeutic agent, offering a potential solution to the limitations of current TB treatment strategies.

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2024-12-16
2025-01-18

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References

  1. Global tuberculosis report 2023. 2023 Available from: https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2023
  2. Desai S.K. Bera S. Mondal D. Gelatin nanoparticles as carrier for effective antituberculosis drug delivery in combination therapy. J. Bionanosci. 2024 10.1007/s12668‑024‑01317‑z
    [Google Scholar]
  3. Kirtane A.R. Verma M. Karandikar P. Furin J. Langer R. Traverso G. Nanotechnology approaches for global infectious diseases. Nat. Nanotechnol. 2021 16 4 369 384 10.1038/s41565‑021‑00866‑8 33753915
    [Google Scholar]
  4. Zegeye A. Dessie G. Wagnew F. Gebrie A. Islam S.M.S. Tesfaye B. Kiross D. Prevalence and determinants of anti-tuberculosis treatment non-adherence in Ethiopia: A systematic review and meta-analysis. PLoS One 2019 14 1 e0210422 10.1371/journal.pone.0210422 30629684
    [Google Scholar]
  5. Pati R. Sahu R. Panda J. Sonawane A. Encapsulation of zinc-rifampicin complex into transferrin-conjugated silver quantum-dots improves its antimycobacterial activity and stability and facilitates drug delivery into macrophages. Sci. Rep. 2016 6 1 24184 10.1038/srep24184 27113139
    [Google Scholar]
  6. Chakraborty P. Bajeli S. Kaushal D. Radotra B.D. Kumar A. Biofilm formation in the lung contributes to virulence and drug tolerance of Mycobacterium tuberculosis Nat. Commun. 2021 12 1 1606 10.1038/s41467‑021‑21748‑6 33707445
    [Google Scholar]
  7. Polyudova T.V. Eroshenko D.V. Pimenova E.V. The biofilm formation of nontuberculous mycobacteria and its inhibition by essential oils. Int. J. Mycobacteriol. 2021 10 1 43 50 10.4103/ijmy.ijmy_228_20 33707371
    [Google Scholar]
  8. Nasiruddin M. Neyaz M.K. Das S. Nanotechnology‐based approach in tuberculosis treatment. Tuberc. Res. Treat. 2017 2017 1 4920209 28210505
    [Google Scholar]
  9. Kia P. Ruman U. Pratiwi A.R. Hussein M.Z. Innovative therapeutic approaches based on nanotechnology for the treatment and management of tuberculosis. Int. J. Nanomedicine 2023 18 1159 1191 10.2147/IJN.S364634 36919095
    [Google Scholar]
  10. Cheung R. Ng T. Wong J. Chan W. Chitosan: An update on potential biomedical and pharmaceutical applications. Mar. Drugs 2015 13 8 5156 5186 10.3390/md13085156 26287217
    [Google Scholar]
  11. Amarnath Praphakar R. Alarfaj A.A. Munusamy M.A. Dusthackeer V.N.A. Kumar Subbiah S. Rajan M. Phosphorylated κ‐carrageenan‐facilitated chitosan nanovehicle for sustainable anti‐tuberculosis multi drug delivery. ChemistrySelect 2017 2 24 7100 7107 10.1002/slct.201701396
    [Google Scholar]
  12. Das B.S. Sarangi A. Sahoo A. Jena B. Patnaik G. Rout S.S. Sahoo S. Bhattacharya D. Studies on phytoconstituents, antioxidant and antimicrobial activity of Trachyspermum ammi seed oil extract with reference to specific foodborne pathogens. J. Essent. Oil-Bear. Plants 2022 25 5 1012 1028 10.1080/0972060X.2022.2132834
    [Google Scholar]
  13. Das B.S. Sarangi A. Rout S.S. Sahoo A. Giri S. Bhattacharya D. Antimycobacterial potential of Trachyspermum ammi seed essential oil via fume contact and determination of major compounds. Nat. Prod. Res. 2024 1 7 10.1080/14786419.2023.2300404 38189354
    [Google Scholar]
  14. Kowalczyk A. Twarowski B. Fecka I. Tuberoso C.I.G. Jerković I. Thymol as a component of chitosan systems - Several new applications in medicine: A comprehensive review. Plants 2024 13 3 362 10.3390/plants13030362 38337895
    [Google Scholar]
  15. Jo E.R. Oh J. Cho S.I. Inhibitory effect of thymol on tympanostomy tube biofilms of methicillin-resistant Staphylococcus aureus and ciprofloxacin-resistant Pseudomonas aeruginosa. Microorganisms 2022 10 9 1867 10.3390/microorganisms10091867 36144469
    [Google Scholar]
  16. Zhou W. Wang Z. Mo H. Zhao Y. Li H. Zhang H. Hu L. Zhou X. Thymol mediates bactericidal activity against Staphylococcus aureus by targeting an aldo-keto reductase and consequent depletion of NADPH. J. Agric. Food Chem. 2019 67 30 8382 8392 10.1021/acs.jafc.9b03517 31271032
    [Google Scholar]
  17. Li Q. Huang K.X. Pan S. Su C. Bi J. Lu X. Thymol disrupts cell homeostasis and inhibits the growth of Staphylococcus aureus. Contrast Media Mol. Imaging 2022 2022 1 8743096 10.1155/2022/8743096 36034206
    [Google Scholar]
  18. Liang C. Huang S. Geng Y. Huang X. Chen D. Lai W. Guo H. Deng H. Fang J. Yin L. Ouyang P. A Study on the antibacterial mechanism of thymol against Aeromonas hydrophila in vitro. Aquacult. Int. 2022 30 1 115 129 10.1007/s10499‑021‑00789‑0
    [Google Scholar]
  19. Bonetti A. Tugnoli B. Piva A. Grilli E. Thymol as an adjuvant to restore antibiotic efficacy and reduce antimicrobial resistance and virulence gene expression in enterotoxigenic Escherichia coli strains. Antibiotics (Basel) 2022 11 8 1073 10.3390/antibiotics11081073 36009942
    [Google Scholar]
  20. Cirino I.C.S. de Santana C.F. Bezerra M.J.R. Rocha I.V. Luz A.C.O. Coutinho H.D.M. de Figueiredo R.C.B.Q. Raposo A. Lho L.H. Han H. Leal-Balbino T.C. Comparative transcriptomics analysis of multidrug-resistant Acinetobacter baumannii in response to treatment with the terpenic compounds thymol and carvacrol. Biomed. Pharmacother. 2023 165 115189 10.1016/j.biopha.2023.115189 37481932
    [Google Scholar]
  21. dos Santos Barbosa C.R. Scherf J.R. de Freitas T.S. de Menezes I.R.A. Pereira R.L.S. dos Santos J.F.S. de Jesus S.S.P. Lopes T.P. de Sousa Silveira Z. de Morais Oliveira-Tintino C.D. Júnior J.P.S. Coutinho H.D.M. Tintino S.R. da Cunha F.A.B. Effect of carvacrol and thymol on nora efflux pump inhibition in multidrug-resistant (MDR) Staphylococcus aureus strains. J. Bioenerg. Biomembr. 2021 53 4 489 498 10.1007/s10863‑021‑09906‑3 34159523
    [Google Scholar]
  22. Piri-Gharaghie T. Beiranvand S. Riahi A. Shirin N.J. Badmasti F. Mirzaie A. Elahianfar Y. Ghahari S. Ghahari S. Pasban K. Hajrasouliha S. Fabrication and characterization of thymol‐loaded chitosan nanogels: Improved antibacterial and anti‐biofilm activities with negligible cytotoxicity. Chem. Biodivers. 2022 19 3 e202100426 10.1002/cbdv.202100426 34989129
    [Google Scholar]
  23. Sheorain J. Mehra M. Thakur R. Grewal S. Kumari S. In vitro anti-inflammatory and antioxidant potential of thymol loaded bipolymeric (tragacanth gum/chitosan) nanocarrier. Int. J. Biol. Macromol. 2019 125 1069 1074 10.1016/j.ijbiomac.2018.12.095 30552929
    [Google Scholar]
  24. Wang Z. Bai H. Lu C. Hou C. Qiu Y. Zhang P. Duan J. Mu H. Light controllable chitosan micelles with ROS generation and essential oil release for the treatment of bacterial biofilm. Carbohydr. Polym. 2019 205 533 539 10.1016/j.carbpol.2018.10.095 30446137
    [Google Scholar]
  25. Ahmady A.R. Razmjooee K. Saber-Samandari S. Toghraie D. Fabrication of chitosan-gelatin films incorporated with thymol-loaded alginate microparticles for controlled drug delivery, antibacterial activity and wound healing: In-vitro and in-vivo studies. Int. J. Biol. Macromol. 2022 223 Part A 567 582 10.1016/j.ijbiomac.2022.10.249
    [Google Scholar]
  26. Olivas-Flores J. Chávez-Méndez J.R. Castillo-Martínez N.A. Sánchez-Pérez H.J. Serrano-Medina A. Cornejo-Bravo J.M. Antimicrobial effect of chitosan nanoparticles and Allium species on Mycobacterium tuberculosis and several other microorganisms. Microorganisms 2024 12 8 1605 10.3390/microorganisms12081605 39203447
    [Google Scholar]
  27. Chittratan P. Chalitangkoon J. Wongsariya K. Mathaweesansurn A. Detsri E. Monvisade P. New chitosan-grafted thymol coated on gold nanoparticles for control of cariogenic bacteria in the oral cavity. ACS Omega 2022 7 30 26582 26590 10.1021/acsomega.2c02776 35936441
    [Google Scholar]
  28. Sarangi A. Das B.S. Rout S.S. Sahoo A. Giri S. Bhattacharya D. Antimycobacterial and antibiofilm activity of garlic essential oil using vapor phase techniques. J. Appl. Biol. 2023 11 1 66 72
    [Google Scholar]
  29. Leena Panigrahi L. Shekhar S. Sahoo B. Arakha M. Adsorption of antimicrobial peptide onto chitosan-coated iron oxide nanoparticles fosters oxidative stress triggering bacterial cell death. RSC Advances 2023 13 36 25497 25507 10.1039/D3RA04070D 37636508
    [Google Scholar]
  30. Buriti B.M.A.B. Figueiredo P.L.B. Passos M.F. da Silva J.K.R. Polymer-based wound dressings loaded with essential oil for the treatment of wounds: A review. Pharmaceuticals (Basel) 2024 17 7 897 10.3390/ph17070897 39065747
    [Google Scholar]
  31. Mohammed-Sadhakathullah A.H.M. Paulo-Mirasol S. Torras J. Armelin E. Advances in functionalization of bioresorbable nanomembranes and nanoparticles for their use in biomedicine. Int. J. Mol. Sci. 2023 24 12 10312 10.3390/ijms241210312 37373461
    [Google Scholar]
  32. Mohamed J.M.M. Alqahtani A. Kumar T.V.A. Fatease A.A. Alqahtani T. Krishnaraju V. Ahmad F. Menaa F. Alamri A. Muthumani R. Vijaya R. Superfast synthesis of stabilized silver nanoparticles using aqueous Allium sativum (garlic) extract and isoniazid hydrazide conjugates: Molecular docking and in-vitro characterizations. Molecules 2021 27 1 110 10.3390/molecules27010110 35011342
    [Google Scholar]
  33. Oluoch G. Matiru V. Mamati E.G. Nyongesa M. Nanoencapsulation of thymol and eugenol with chitosan nanoparticles and the effect against Ralstonia solanacearum. Adv. Microbiol. 2021 11 12 723 739 10.4236/aim.2021.1112052
    [Google Scholar]
  34. Ghasemi M. Turnbull T. Sebastian S. Kempson I. The MTT assay: Utility, limitations, pitfalls, and interpretation in bulk and single-cell analysis. Int. J. Mol. Sci. 2021 22 23 12827 10.3390/ijms222312827 34884632
    [Google Scholar]
  35. Xu C. Akakuru O.U. Zheng J. Wu A. Applications of iron oxide-based magnetic nanoparticles in the diagnosis and treatment of bacterial infections. Front. Bioeng. Biotechnol. 2019 7 141 10.3389/fbioe.2019.00141 31275930
    [Google Scholar]
  36. Sharifi E. Reisi F. Yousefiasl S. Elahian F. Barjui S.P. Sartorius R. Fattahi N. Zare E.N. Rabiee N. Gazi E.P. Paiva-Santos A.C. Parlanti P. Gemmi M. Mobini G-R. Hashemzadeh-Chaleshtori M. De Berardinis P. Sharifi I. Mattoli V. Makvandi P. Chitosan decorated cobalt zinc ferrite nanoferrofluid composites for potential cancer hyperthermia therapy: Anti-cancer activity, genotoxicity, and immunotoxicity evaluation. Adv. Compos. Hybrid Mater. 2023 6 6 191 10.1007/s42114‑023‑00768‑4
    [Google Scholar]
  37. Zuniga E.S. Early J. Parish T. The future for early-stage tuberculosis drug discovery. Future Microbiol. 2015 10 2 217 229 10.2217/fmb.14.125 25689534
    [Google Scholar]
  38. Chen C.C. Chen Y.Y. Yeh C.C. Hsu C.W. Yu S.J. Hsu C.H. Wei T.C. Ho S.N. Tsai P.C. Song Y.D. Yen H.J. Chen X.A. Young J.J. Chuang C.C. Dou H.Y. Alginate-capped silver nanoparticles as a potent anti-mycobacterial agent against mycobacterium tuberculosis. Front. Pharmacol. 2021 12 746496 10.3389/fphar.2021.746496 34899300
    [Google Scholar]
  39. Kowalczyk A. Przychodna M. Sopata S. Bodalska A. Fecka I. Thymol and thyme essential oil - New insights into selected therapeutic applications. Molecules 2020 25 18 4125 10.3390/molecules25184125 32917001
    [Google Scholar]
  40. Basavegowda N. Baek K.H. Combination strategies of different antimicrobials: An efficient and alternative tool for pathogen inactivation. Biomedicines 2022 10 9 2219 10.3390/biomedicines10092219 36140320
    [Google Scholar]
  41. Haghniaz R. Rabbani A. Vajhadin F. Khan T. Kousar R. Khan A.R. Montazerian H. Iqbal J. Libanori A. Kim H.J. Wahid F. Anti‐bacterial and wound healing‐promoting effects of zinc ferrite nanoparticles. J. Nanobiotechnology 2021 19 1 38 10.1186/s12951‑021‑00776‑w 33546702
    [Google Scholar]
  42. Aisida S.O. Gospel E.C. Alshoaibi A. Okeudo D. Ijeh R. Ezema F.I. Effect of chitosan on the microstructural properties of zinc ferrite nanoparticles. Macromol. Chem. Phys. 2024 225 6 2300375 10.1002/macp.202300375
    [Google Scholar]
  43. Mohsen A.M. Nagy Y.I. Shehabeldine A.M. Okba M.M. Thymol-Loaded Eudragit RS30D cationic nanoparticles-based hydrogels for topical application in wounds: In vitro and in vivo evaluation. Pharmaceutics 2022 15 1 19 10.3390/pharmaceutics15010019 36678648
    [Google Scholar]
  44. Zhang H. Mardyani S. Chan W.C.W. Kumacheva E. Design of biocompatible chitosan microgels for targeted pH-mediated intracellular release of cancer therapeutics. Biomacromolecules 2006 7 5 1568 1572 10.1021/bm050912z 16677040
    [Google Scholar]
  45. Shetta A. Kegere J. Mamdouh W. Comparative study of encapsulated peppermint and green tea essential oils in chitosan nanoparticles: Encapsulation, thermal stability, in-vitro release, antioxidant and antibacterial activities. Int. J. Biol. Macromol. 2019 126 731 742 10.1016/j.ijbiomac.2018.12.161 30593811
    [Google Scholar]
  46. Behzadi S. Serpooshan V. Tao W. Hamaly M.A. Alkawareek M.Y. Dreaden E.C. Brown D. Alkilany A.M. Farokhzad O.C. Mahmoudi M. Cellular uptake of nanoparticles: Journey inside the cell. Chem. Soc. Rev. 2017 46 14 4218 4244 10.1039/C6CS00636A 28585944
    [Google Scholar]
  47. Sarangi A. Singh S.P. Das B.S. Rajput S. Fatima S. Bhattacharya D. Mycobacterial biofilms: A therapeutic target against bacterial persistence and generation of antibiotic resistance. Heliyon 2024 10 11 e32003 10.1016/j.heliyon.2024.e32003 38882302
    [Google Scholar]
  48. Chandra P. Grigsby S.J. Philips J.A. Immune evasion and provocation by Mycobacterium tuberculosis. Nat. Rev. Microbiol. 2022 20 12 750 766 10.1038/s41579‑022‑00763‑4 35879556
    [Google Scholar]
  49. Ojha A.K. Baughn A.D. Sambandan D. Hsu T. Trivelli X. Guerardel Y. Alahari A. Kremer L. Jacobs W.R. Hatfull G.F. Growth of Mycobacterium tuberculosis biofilms containing free mycolic acids and harbouring drug‐tolerant bacteria. Mol. Microbiol. 2008 69 1 164 174 10.1111/j.1365‑2958.2008.06274.x 18466296
    [Google Scholar]
  50. Liu X. Hu J. Wang W. Yang H. Tao E. Ma Y. Sha S. Mycobacterial biofilm: Mechanisms, clinical problems, and treatments. Int. J. Mol. Sci. 2024 25 14 7771 10.3390/ijms25147771 39063012
    [Google Scholar]
  51. Salina E.G. Makarov V. Mycobacterium tuberculosis dormancy: How to fight a hidden danger. Microorganisms 2022 10 12 2334 10.3390/microorganisms10122334 36557586
    [Google Scholar]
/content/journals/ctmc/10.2174/0115680266348684241211072446
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Thymol-Loaded Zinc Ferrite Nanoparticles: A Novel Carrier for 
Enhanced Antimicrobial and Antibiofilm Activity against M. smegmatis through ROS-Mediated Mechanism
Bentham Science Publishers ; https://doi.org/10.2174/0115680266348684241211072446
/content/journals/ctmc/10.2174/0115680266348684241211072446
/content/journals/ctmc/10.2174/0115680266348684241211072446
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  • Article Type:     Research Article
Keywords: nutrient starvation activity ; ROS activity ; M. smegmatis ; conjugate zinc ferrite NPs ; anti-biofilm activity ; Thymol

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