Green Synthesized Silver Nanoparticles Loaded with Isoniazid for Enhanced Anti-Mycobacterial Activity
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Abstract
Background: Tuberculosis remains a major infectious disease worldwide, and the increasing emergence of drug-resistant strains has reduced the effectiveness of conventional treatment strategies. Isoniazid is an important first-line anti-tuberculosis drug; however, resistance development and limited drug delivery remain significant challenges. Nanotechnology-based approaches, particularly green synthesized metal nanoparticles, have gained attention due to their antimicrobial properties and potential to improve drug performance. Objective: The present study aimed to develop a plant-mediated silver nanoparticle formulation loaded with isoniazid and evaluate its physicochemical characteristics, anti-mycobacterial activity, stability, and safety profile for potential application against resistant tuberculosis strains. Methods: Silver nanoparticles were synthesized using a green plant extract approach under controlled laboratory conditions. The synthesized nanoparticles were loaded with isoniazid and characterized using UV–Visible spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, electron microscopy, and particle size analysis. The antimicrobial potential of free isoniazid, silver nanoparticles, and isoniazid-loaded silver nanoparticles was evaluated against Mycobacterium tuberculosis. Drug stability and toxicity assessment were also performed to determine the suitability of the developed formulation. Results: The green synthesis process successfully produced stable silver nanoparticles, confirmed through characteristic optical and structural analyses. The incorporation of isoniazid resulted in increased nanoparticle size and maintained formulation stability. The isoniazid-loaded silver nanoparticles demonstrated stronger anti-mycobacterial activity compared with individual treatments, indicating an improved therapeutic effect through combined nanoparticle and drug action. The formulation showed acceptable compatibility during toxicity evaluation while maintaining antimicrobial effectiveness. Conclusion: The findings suggest that plant-mediated silver nanoparticles loaded with isoniazid may provide a promising strategy for enhancing anti-mycobacterial activity and improving drug delivery against tuberculosis. This nano-based formulation could offer a potential alternative approach for addressing limitations associated with conventional therapy and drug resistance. Further in vivo studies and clinical investigations are recommended to evaluate its therapeutic applicability.
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References
1. World Health Organization. Global tuberculosis report 2023. Geneva: WHO; 2023.https://www.who.int/teams/global-tuberculosis-programme/tb-reports
2. Pai M, Kasaeva T, Swaminathan S. Tuberculosis control: WHO perspective and beyond. Nat Rev Dis Primers. 2016;2:16084. doi:
3. https://doi.org/10.1038/nrdp.2016.84
4. Dheda K, Barry CE, Maartens G. Tuberculosis. Lancet. 2016;387(10024):1211–1226. doi: https://doi.org/10.1016/S0140-6736(15)00151-8
5. Lange C, Dheda K, Chesov D, Mandalakas AM, Udwadia Z, Horsburgh CR Jr. Management of drug-resistant tuberculosis. Lancet. 2019;394(10202):953–966. doi: https://doi.org/10.1016/S0140-6736(19)31882-3
6. Khan A, Fahad S, Faisal S, et al. Tuberculosis burden and challenges in Pakistan: current situation and future perspectives. J Infect Dev Ctries. 2021;15(8):1071–1078. doi: https://doi.org/10.3855/jidc.14563
7. Raviglione MC, Uplekar MW. WHO's new Stop TB Strategy. Lancet. 2006;367(9514):952–955. doi: https://doi.org/10.1016/S0140-6736(06)68392-X
8. Rai M, Yadav A, Gade A. Silver nanoparticles as a new generation of antimicrobials. Biotechnol Adv. 2009;27(1):76–83. doi: https://doi.org/10.1016/j.biotechadv.2008.09.002
9. Durán N, Durán M, de Jesus MB, Seabra AB, Fávaro WJ, Nakazato G. Silver nanoparticles: a new view on mechanistic aspects on antimicrobial activity. Nanomedicine. 2016;12(3):789–799. doi: https://doi.org/10.1016/j.nano.2015.11.016
10. Burdușel AC, Gherasim O, Grumezescu AM, Mogoantă L, Ficai A, Andronescu E. Biomedical applications of silver nanoparticles: an up-to-date overview. Nanomaterials. 2018;8(9):681. doi:
11. https://doi.org/10.3390/nano8090681
12. Ahmed S, Ahmad M, Swami BL, Ikram S. A review on plants extract mediated synthesis of silver nanoparticles. J Adv Res. 2016;7(1):17–28. doi: https://doi.org/10.1016/j.jare.2015.02.007
13. Iravani S. Green synthesis of metal nanoparticles using plants. Green Chem. 2011;13:2638–2650. doi: https://doi.org/10.1039/C1GC15386B
14. Makarov VV, Love AJ, Sinitsyna OV, et al. Green nanotechnologies: synthesis of metal nanoparticles using plants. Acta Naturae. 2014;6(1):35–44. doi: https://doi.org/10.32607/20758251-2014-6-1-35-44
15. Sondi I, Salopek-Sondi B. Silver nanoparticles as antimicrobial agent. J Colloid Interface Sci. 2004;275(1):177–182. doi: https://doi.org/10.1016/j.jcis.2004.02.012
16. Prabhu S, Poulose EK. Silver nanoparticles: mechanism of antimicrobial action, synthesis, medical applications. Asian Pac J Trop Biomed. 2012;2(1):S1–S7. doi:
17. https://doi.org/10.1016/S2221-1691(12)70002-4
18. Wang L, Hu C, Shao L. The antimicrobial activity of nanoparticles: present situation and prospects. Int J Nanomedicine. 2017;12:1227–1249. doi:
19. https://doi.org/10.2147/IJN.S121956
20. Paladini F, Pollini M. Antimicrobial silver nanoparticles for wound healing application: progress and future prospects. Materials. 2019;12(16):2540. doi:
21. https://doi.org/10.3390/ma12162540
22. Bapat RA, Chaubal TV, Joshi CP, et al. An overview of application of silver nanoparticles for antimicrobial activity. J Nanobiotechnology. 2018;16:52. doi:
23. https://doi.org/10.1186/s12951-018-0380-8
24. Hwang IS, Hwang JH, Choi H, et al. Silver nanoparticles induce oxidative stress and antimicrobial effects. Appl Environ Microbiol. 2012;78(5):1564–1570. doi: https://doi.org/10.1128/AEM.07423-11
25. Dakal TC, Kumar A, Majumdar RS, Yadav V. Mechanistic basis of antimicrobial actions of silver nanoparticles. Front Microbiol. 2016;7:1831. doi: https://doi.org/10.3389/fmicb.2016.01831
26. Mishra A, Tripathi K, Singh S, et al. Nanotechnology-based approaches against tuberculosis. Int J Nanomedicine. 2021;16:6829–6847. doi: https://doi.org/10.2147/IJN.S318932
27. Pandey R, Zahoor A. Nanomedicine approaches for tuberculosis treatment. Drug Deliv Transl Res. 2020;10:1096–1110. doi: https://doi.org/10.1007/s13346-020-00757-5
28. Gelperina S, Nanoparticulate systems for drug delivery to tuberculosis infection sites. J Control Release. 2005;107(3):279–293. doi: https://doi.org/10.1016/j.jconrel.2005.06.004
29. Kaur P, Kaur S, Singh M. Nanotechnology approaches for tuberculosis diagnosis and treatment. Biomed Pharmacother. 2022;146:112548. doi: https://doi.org/10.1016/j.biopha.2021.112548
30. Larsen MH, Vilchèze C, Kremer L, et al. Overexpression of isoniazid resistance mechanisms in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2002;46(12):3684–3690. doi: https://doi.org/10.1128/AAC.46.12.3684-3690.2002
31. Vilchèze C, Jacobs WR Jr. The mechanism of isoniazid action and resistance in Mycobacterium tuberculosis. Annu Rev Microbiol. 2007;61:35–50. doi: https://doi.org/10.1146/annurev.micro.61.080706.093425