Abstract
In the present study, usnic acid (UA) nanoparticles (NPs) are synthesized and loaded on the 2D structure of graphene (GN) by the physio-sorption technique. This UA-GN nanoconjugate was then suspended in the water-soluble ointment base and evaluated for antibacterial activity. Antimicrobial drugs and NPs can be used together against antibiotic resistance; this would facilitate the unique mechanism to kill the pathogens that are resistant to the antibiotics. The unique mechanism where GN raptures the cell wall of microbes and then UA penetrates into the cell wall and disrupts the metabolic function of the cell and thus cuts the energy power led to cell death. This unique method of bacterial cell death is limited to the affected area because it is applied in the form of topical preparations. The UA, NPs, and GN all together show a synergistic effect against gram-positive and gram-negative pathogens. In the current study, nano-ointment of usnic acid NP’s graphene nanoconjugate (UGNC) showed an enhanced effect to kill the pathogens with the triple action of combination therapy with US, NPs, and their conjugate with GN. In vivo antibacterial activity of UGNC nano-ointment on Wistar albino rats shows a significant positive outcome despite hindrance in the in vitro dissolution profile, and it is better that the marketed formulation has the steroid.
Similar content being viewed by others
Data Availability
Not applicable.
Code Availability
Not applicable.
References
Murray, C. J. L. (2020). Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: A systematic analysis for the Global Burden of Disease Study 2019. The Lancet, 396(10258), 629–655.
Periyasamy, P. C., Leijten, J. C., Hermanus, J. P., & Johannes, P. J. (2012). Nanomaterials for the local and targeted delivery of osteoarthritis drugs. Journal of nanomaterials, 12, 673–687.
Levin, B. R., & Antia, R. (2001). Why we don’t get sick: The within-host population dynamics of bacterial infections. Science, 292, 1112–1115.
Rizzello, L., & Pompa, P. P. (2014). Nanosilver-based antibacterial drugs and devices: Mechanisms, methodological drawbacks, and guidelines. Chemical Society Reviews, 43, 1501–1518.
Kirk, M. D., Pires, S. M., Black, R. E., Caipo, M., Crump, J. A., Devleesschauwer, B., Döpfer, D., Fazil, A., Fischer-Walker, C. L., Hald, T., Hall, A. J., Keddy, K. H., Lake, R. J., Lanata, C. F., Torgerson, P. R., Havelaar, A. H., & Angulo, F. J. (2015). World Health Organization estimates of the global and regional disease burden of 22 foodborne bacterial, protozoal, and viral diseases. A Data Synthesis, 12(12), 14.
Blair, J. M., Webber, M. A., Baylay, A. J., Ogbolu, D. O., & Piddock, L. J. (2015). Molecular mechanisms of antibiotic resistance. Nature Reviews Microbiology, 1(13), 42–51.
Moritz, M., & Geszke-Moritz, M. (2013). The newest achievements in synthesis, immobilization and practical applications of antibacterial nanoparticles. Chemical Engineering Journal, 228, 596–613.
Hibbing, M. E., Fuqua, C., Parsek, M. R., & Peterson, S. B. (2010). Bacterial competition: Surviving and thriving in the microbial jungle. Nat Rev Microbiol, 8(1), 15–25.
Liu, Y., Wang, X., Yang, F., & Yang, X. (2008). Excellent antimicrobial properties of mesoporous anatase TiO2 and Ag/TiO2 composite films. Microporous and Mesoporous Materials, 114, 431–439.
Pandey, H., Parashar, V., Parashar, R., Prakash, R., Ramteke, P. W., & Pandey, A. C. (2011). Controlled drug release characteristics and enhanced antibacterial effect of graphene nanosheets containing gentamicin sulfate. Nanoscale, 3(10), 4104–8.
Jia, Z., Shen, D., & Xu, W. (2001). Synthesis and antibacterial activities of quaternary ammonium salt of chitosan. Carbohydrate Research, 333(1), 333.
Wang, L., Chen, J., Shi, L., Shi, Z., Ren, L., & Wang, Y. (2014). The promotion of antimicrobial activity on silicon substrates using a “click” immobilized short peptide. Chemical Communications (Camb), 50(8), 975–7.
Rana, D., & Matsuura, T. (2010). Surface modifications for antifouling membranes. Chemical Reviews, 110(4), 2448–71.
Lok, C. N., Chen, R., He, Q. Y., Yu, W. Y., Sun, H., Tam, P. K., Chiu, J. F., & Che, C. M. (2006). Proteomic analysis of the mode of antibacterial action of silver nanoparticles. Journal of Proteome Research, 5(4), 916–24.
Ahamed, M., Alsalhi, M. S., & Siddiqui, M. K. (2010). Silver nanoparticle applications and human health. Clinica Chimica Acta, 411(23–24), 1841–8.
Kümmerer, K. (2004). Resistance in the environment. Journal of Antimicrobial Chemotherapy, 54(2), 311–320.
Yeaman, M. R., & Yount, N. Y. (2003). Mechanisms of antimicrobial peptide action and resistance. Pharmacological Reviews, 55(1), 27–55.
McLean, D. T., Lundy, F. T., & Timson, D. J. (2013). IQ-motif peptides as novel anti-microbial agents. Biochimie, 95(4), 875–80.
Kumar, A., Vemula, P. K., Ajayan, P. M., & John, G. (2008). Silver-nanoparticle-embedded antimicrobial paints based on vegetable oil. Nature Materials, 7(3), 236–41.
Wei, C., Lin, W. Y., Zainal, Z., Williams, N. E., Zhu, K., Kruzic, A. P., Smith, R. L., & Rajeshwar, K. (1994). Bactericidal activity of TiO2 photocatalyst in aqueous media: Toward a solar-assisted water disinfection system. Environmental Science & Technology, 28(5), 934–8.
Alahmadi, A. A. (2017). Usnic acid biological activity: History, evaluation and usage. International Journal of Basic & Clinical Pharmacology, 6(12), 2752–59.
Mishra, S. B., Pandey, H., & Pandey, A. C. (2013). “Nanosuspension of Phyllanthus amarus extract for improving oral bioavailability and prevention of paracetamol induced hepatotoxicity in Sprague-Dawley rats. Advances in Natural Sciences: Nanoscience and Nanotechnology, 4, 035007.
Maru, A. D., & Lahoti, S. R. (2019). Formulation and evaluation of ointment containing Sunflower wax. Asian Journal of Pharmaceutical and Clinical Research, 12(8), 115–20.
Karthikeyini, S. C., Pandian, M. S., & Nagarajan, M. (2017). Fabrication, characterization and pharmacological activity of usnic acid loaded nanoparticles. IJPSR, 8(11), 4758–4766.
Thomas, R., Nair, A. P., Soumya, K. R., Mathew, J., & Radhakrishnan, E. K. (2014). Antibacterial activity and synergistic effect of biosynthesized groups with antibiotics against multidrug-resistant biofilm- forming coagulase-negative staphylococci isolated from clinical samples. Applied Biochemistry and Biotechnology, 173, 449–460.
Acknowledgements
The authors are grateful to the United Institute of Pharmacy, Prayagraj, for providing an animal house facility to accommodate the animals and carrying out the pharmacological activity and to the Institute of Pharmacy, Dr. A.P.J. Abdul Kalam University, for supervising the interpretation of the data.
Funding
The authors did not receive support from any organization for the submitted work.
Author information
Authors and Affiliations
Contributions
PKV has worked on the all-experimental work and written the manuscript. RAG and SBM have supervised and reviewed all experimental work and statistical analysis. GJ and KhV have prepared figures and graphics. All authors reviewed the manuscript.
Corresponding author
Ethics declarations
Conflict of Interest
None.
Research Involving Humans and Animals
Authors have followed all applicable international, national and/or institutional guidelines for the care and use of animals. The animal studies were accomplished according to CPCSEA guidelines. The animal studies were approved (Approval No. UIP/IAEC/Sept-2020/07) by the IAEC of the United Institute of Pharmacy, Prayagraj, India.
Informed Consent
None.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Highlights
The concept of this fundamental research is to breach the pathogen’s cell walls and then deliver the antimicrobial drugs to their cells, leading to cell death.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Vishwakarma, P.K., Gupta, R.A., Jain, G. et al. Supertool for Superbugs—Smart “Nano-ointment of Graphene Usnic Acid Nanoparticles” Against Antimicrobial Resistance (AMRs). BioNanoSci. 13, 1231–1242 (2023). https://doi.org/10.1007/s12668-023-01153-7
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12668-023-01153-7