Skip to main content
SpringerLink
Log in

Antimicrobial and antibiofilm activity of curcumin-silver nanoparticles with improved stability and selective toxicity to bacteria over mammalian cells

  • Original Investigation
  • Published:
Medical Microbiology and Immunology Aims and scope Submit manuscript

Abstract

Antibiotic resistance has necessitated search for new antibacterials for combating threat of pathogenic bacteria. Though chemically synthesized silver nanoparticles are a well-known antimicrobial agent, they are toxic to human cells at higher concentrations. Hence in the present study, curcumin-silver nanoparticles (Cur–AgNPs) of size 25–35 nm, were synthesized using curcumin, a phytochemical. These nanoparticles were effective against both Gram positive and Gram-negative bacteria and were less toxic to human keratinocytes. They had very low total silver content and high stability. The antibacterial activity of Cur–AgNPs, as studied by minimum inhibitory concentration (MIC = 5 mg/L), time kill kinetics and post agent effect, was better than silver nanoparticles (AgNPs, size ≈ 35 nm, MIC = 20 mg/L). The inhibitory effect of Cur–AgNPs on biofilm formation was also ≈ 20% more than AgNPs as demonstrated by live–dead imaging and scanning electron microscopy. The cytotoxic test to skin keratinocytes (HaCaT) showed that Cur–AgNPs were toxic at a concentration of 156 mg/L which is much higher than the bacterial MIC (selective toxicity). They also showed anti-inflammatory effect on human macrophages (THP1) by reducing secretion of pro-inflammatory cytokines IL-6 and TNF-α as compared to chemically synthesized AgNPs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. WHO (2017) Methods and data sources for global burden of disease estimates

  2. Aspevall O, Chowdhary T, Eremin S et al (2015) Global antimicrobial resistance surveillance system: manual for early implementation. WHO :1–36

  3. Lee SM, Lee SH (1994) Generalized argyria after habitual use of AgNO3. J Dermatol 21:50–53

    Article  CAS  PubMed  Google Scholar 

  4. Zhou Y, Kong Y, Kundu S et al (2012) Antibacterial activities of gold and silver nanoparticles against Escherichia coli and bacillus Calmette-Guérin. J Nanobiotechnol 10:19

    Article  CAS  Google Scholar 

  5. Desireddy A, Conn BE, Guo J et al (2013) Ultrastable silver nanoparticles. Nature 501:399–402

    Article  CAS  PubMed  Google Scholar 

  6. Foldbjerg R, Dang DA, Autrup H (2011) Cytotoxicity and genotoxicity of silver nanoparticles in the human lung cancer cell line, A549. Arch Toxicol 85:743–750

    Article  CAS  PubMed  Google Scholar 

  7. Grunkemeier G, Jin R, Im K et al (2006) Time-related risk of the St. Jude Silzone heart valve. Eur J Cardio-Thoracic Surg 30:20–27

    Article  Google Scholar 

  8. Morones-Ramirez JR, Winkler JA, Spina CS, Collins JJ (2013) Silver enhances antibiotic activity against gram-negative bacteria. Sci Transl Med 5:997–1003

    Article  Google Scholar 

  9. Mun S-H, Joung D-K, Kim Y-SY-C et al (2013) Synergistic antibacterial effect of curcumin against methicillin-resistant Staphylococcus aureus. Phytomedicine 20:714–718

    Article  CAS  PubMed  Google Scholar 

  10. Zandi K, Ramedani E, Mohammadi K et al (2010) Evaluation of antiviral activities of curcumin derivatives against HSV-1 in Vero cell line. Nat Prod Commun 5:1935–1938

    CAS  PubMed  Google Scholar 

  11. Jurenka JS (2009) Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Altern Med Rev 14:141–153

    PubMed  Google Scholar 

  12. Packiavathy IASV, Priya S, Pandian SK, Ravi AV (2014) Inhibition of biofilm development of uropathogens by curcumin—an anti-quorum sensing agent from Curcuma longa. Food Chem 148:453–460

    Article  CAS  PubMed  Google Scholar 

  13. Naksuriya O, Okonogi S, Schiffelers RM, Hennink WE (2014) Curcumin nanoformulations: A review of pharmaceutical properties and preclinical studies and clinical data related to cancer treatment. Biomaterials 35:3365–3383

    Article  CAS  PubMed  Google Scholar 

  14. Wang Y-J, Pan M-H, Cheng A-L et al (1997) Stability of curcumin in buffer solutions and characterization of its degradation products. J Pharm Biomed Anal 15:1867–1876

    Article  CAS  PubMed  Google Scholar 

  15. Tonnesen HH, Karlsen J (1985) Studies on curcumin and curcuminoids VI. Kinetics of curcumin degradation in aqueous solution. Z Leb Unters Forsch 180:402–404

    Article  CAS  Google Scholar 

  16. Sathishkumar M, Sneha K, Yun YS (2010) Immobilization of silver nanoparticles synthesized using Curcuma longa tuber powder and extract on cotton cloth for bactericidal activity. Bioresour Technol 101:7958–7965

    Article  CAS  PubMed  Google Scholar 

  17. Vimala K, Yallapu MM, Varaprasad K et al (2011) Fabrication of curcumin encapsulated chitosan-PVA silver nanocomposite films for improved antimicrobial activity. J Biomater Nanobiotechnol 2:55–64

    Article  CAS  Google Scholar 

  18. Varaprasad K, Mohan YM, Vimala K, Raju KM (2011) Synthesis and characterization of hydrogel–silver nanoparticle-curcumin composites for wound dressing and antibacterial application. J Appl Polym Sci 121:784–796

    Article  CAS  Google Scholar 

  19. Ravindra S, Mulaba-Bafubiandi AF, Rajinikanth V et al (2012) Development and characterization of curcumin loaded silver nanoparticle hydrogels for antibacterial and drug delivery applications. J Inorg Organomet Polym Mater 22:1254–1262

    Article  CAS  Google Scholar 

  20. Shameli K, Ahmad MB, Shabanzadeh P et al (2014) Effect of Curcuma longa tuber powder extract on size of silver nanoparticles prepared by green method. Res Chem Intermed 40:1313–1325

    Article  CAS  Google Scholar 

  21. El Khoury E, Abiad M, Kassaify ZG, Patra D (2015) Green synthesis of curcumin conjugated nanosilver for the applications in nucleic acid sensing and anti-bacterial activity. Colloids Surf B Biointerfaces 127:274–280

    Article  PubMed  Google Scholar 

  22. Yang XX, Li CM, Huang CZ (2016) Curcumin modified silver nanoparticles for highly efficient inhibition of respiratory syncytial virus infection. Nanoscale 8:3040–3048

    Article  CAS  PubMed  Google Scholar 

  23. Loo CY, Rohanizadeh R, Young PM et al (2016) Combination of silver nanoparticles and curcumin nanoparticles for enhanced anti-biofilm activities. J Agric Food Chem 64:2513–2522

    Article  CAS  PubMed  Google Scholar 

  24. Turkevich J, Stevenson PC, Hillier J (1951) A study of the nucleation and growth processes in the synthesis of colloidal gold. Discuss Faraday Soc 55:55–75

    Article  Google Scholar 

  25. CLSI (2015) Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. CLSI document M07-A8. Clinical and Laboratory Standards Institute, Wayne

    Google Scholar 

  26. EUCAST (2000) Determination of minimum inhibitory concentrations (MICs) of antibacterial agents by agar dilution. EUCAST Definitive Document E Def 3.1. Clin Microbiol Infect 6:509–515

    Article  Google Scholar 

  27. Stubbings WJ, Bostock JM, Ingham E, Chopra I (2004) Assessment of a microplate method for determining the post-antibiotic effect in Staphylococcus aureus and Escherichia coli. J Antimicrob Chemother 54:139–143

    Article  CAS  PubMed  Google Scholar 

  28. Inbakandan D, Kumar C, Abraham LS et al (2013) Silver nanoparticles with anti microfouling effect: A study against marine biofilm forming bacteria. Colloids Surf B Biointerfaces 111:636–643

    Article  CAS  PubMed  Google Scholar 

  29. Mohan PRK, Sreelakshmi G, Muraleedharan CV, Joseph R (2012) Water soluble complexes of curcumin with cyclodextrins: characterization by FT-Raman spectroscopy. Vib Spectrosc 62:77–84

    Article  CAS  Google Scholar 

  30. Kolev TM, Velcheva EA, Stamboliyska BA, Spiteller M (2005) DFT and experimental studies of the structure and vibrational spectra of curcumin. Int J Quantum Chem 102:1069–1079

    Article  CAS  Google Scholar 

  31. Kundu S, Nithiyanantham U (2013) In situ formation of curcumin stabilized shape-selective Ag nanostructures in aqueous solution and their pronounced SERS activity. RSC Adv 3:25278

    Article  CAS  Google Scholar 

  32. Sudhakar C, Selvam K, Govarthanan M et al (2015) Acorus calamus rhizome extract mediated biosynthesis of silver nanoparticles and their bactericidal activity against human pathogens. J Genet Eng Biotechnol 13:93–99

    Article  Google Scholar 

  33. Kittler S, Greulich C, Diendorf J et al (2010) Toxicity of silver nanoparticles increases during storage because of slow dissolution under release of silver ions. Chem Mater 22:4548–4554

    Article  CAS  Google Scholar 

  34. Guzmán M, Dille J, Godet S (2009) Synthesis of silver nanoparticles by chemical reduction method and their antibacterial activity. Int J Chem Biomol Eng 2:104–111

    Google Scholar 

  35. Guzman M, Dille J, Godet S (2012) Synthesis and antibacterial activity of silver nanoparticles against gram-positive and gram-negative bacteria. Nanomed Nanotechnol Biol Med 8:37–45

    Article  CAS  Google Scholar 

  36. Palanisamy NK, Ferina N, Amirulhusni AN et al (2014) Antibiofilm properties of chemically synthesized silver nanoparticles found against Pseudomonas aeruginosa. J Nanobiotechnol 12:2

    Article  Google Scholar 

  37. Panacek A, Kvítek L, Prucek R et al (2006) Silver colloid nanoparticles: synthesis, characterization, and their antibacterial activity. J Phys Chem B 110:16248–16253

    Article  CAS  PubMed  Google Scholar 

  38. Yoon K-Y, Byeon JH, Park J-H et al (2007) Susceptibility constants of Escherichia coli and Bacillus subtilis to silver and copper nanoparticles. Sci Total Environ 373:572–575

    Article  CAS  PubMed  Google Scholar 

  39. Jain J, Arora S, Rajwade JM et al (2009) Silver nanoparticles in therapeutics: development of an antimicrobial gel formulation for topical use. Mol Pharm 6:1388–1401

    Article  CAS  PubMed  Google Scholar 

  40. Kvítek L, Panáček A, Soukupová J et al (2008) Effect of surfactants and polymers on stability and antibacterial activity of silver nanoparticles (NPs). J Phys Chem C 112:5825–5834

    Article  Google Scholar 

  41. Traub WH, Leonhard B (1995) Heat stability of the antimicrobial activity of sixty-two antibacterial agents. J Antimicrob Chemother 35:149–154

    Article  CAS  PubMed  Google Scholar 

  42. Bragg PD, Rainnie D (1974) The effect of silver ions on the respiratory chain of Escherichia coli. Can J Microbiol 20:883–889

    Article  CAS  PubMed  Google Scholar 

  43. Feng QL, Wu J, Chen GQ et al (2000) A mechanistic study of the antibacterial effect of silver ions on Escherichia coli and Staphylococcus aureus. J Biomed Mater Res 52:662–668

    Article  CAS  PubMed  Google Scholar 

  44. Wakamoto Y, Dhar N, Chait R et al (2013) Dynamic persistence of antibiotic-stressed mycobacteria. Science 339 (80):91–95

    Article  CAS  PubMed  Google Scholar 

  45. Diard M, Sellin ME, Dolowschiak T et al (2014) Antibiotic treatment selects for cooperative virulence of Salmonella typhimurium. Curr Biol 24:2000–2005

    Article  CAS  PubMed  Google Scholar 

  46. Namasivayam SKR, Christo BB, Arasu SMK et al (2013) Anti biofilm effect of biogenic silver nanoparticles coated medical devices against biofilm of clinical isolate of Staphylococcus aureus. Glob J Med Res. 13

  47. Mohanty S, Mishra S, Jena P et al (2012) An investigation on the antibacterial, cytotoxic, and antibiofilm efficacy of starch-stabilized silver nanoparticles. Nanomed Nanotech Biol Med 8:916–924

    Article  CAS  Google Scholar 

  48. Krupa AND, Raghavan V (2014) Biosynthesis of silver nanoparticles using Aegle marmelos (Bael) fruit extract and its application to prevent adhesion of bacteria: a strategy to control microfouling. Bioinorg Chem Appl 2014:949538

    Google Scholar 

  49. Choi O, Yu CP, Esteban Fernández G, Hu Z (2010) Interactions of nanosilver with Escherichia coli cells in planktonic and biofilm cultures. Water Res 44:6095–6103

    Article  CAS  PubMed  Google Scholar 

  50. Kanmani P, Lim ST (2013) Synthesis and characterization of pullulan-mediated silver nanoparticles and its antimicrobial activities. Carbohydr Polym 97:421–428

    Article  CAS  PubMed  Google Scholar 

  51. Namasivayam SKR, Preethi M, Bharani. R. S A et al (2012) Biofilm inhibitory effect of silver nanoparticles coated catheter against Staphylococcus aureus and evaluation of its synergistic effects with antibiotics. Int J Biol Pharm Res 3:259–265

    Google Scholar 

  52. Kulkarni RR, Shaiwale NS, Deobagkar DN, Deobagkar DD (2015) Synthesis and extracellular accumulation of silver nanoparticles by employing radiation-resistant Deinococcus radiodurans, their characterization, and determination of bioactivity. Int J Nanomed 10:963–974

    Google Scholar 

  53. Zhao L, Wang H, Huo K et al (2011) Antibacterial nano-structured titania coating incorporated with silver nanoparticles. Biomaterials 32:5706–5716

    Article  CAS  PubMed  Google Scholar 

  54. Ribble D, Goldstein NB, Norris D a, Shellman YG (2005) A simple technique for quantifying apoptosis in 96-well plates. BMC Biotechnol 5:12

    Article  PubMed  PubMed Central  Google Scholar 

  55. Rybtke M, Hultqvist LD, Givskov M, Tolker-Nielsen T (2015) Pseudomonas aeruginosa biofilm infections: community structure, antimicrobial tolerance and immune response. J Mol Biol 427:3628–3645

    Article  CAS  PubMed  Google Scholar 

  56. Bodelón G, Montes-García V, López-Puente V et al (2016) Detection and imaging of quorum sensing in Pseudomonas aeruginosa biofilm communities by surface-enhanced resonance Raman scattering. Nat Mater 15:1203–1211

    Article  PubMed  PubMed Central  Google Scholar 

  57. Wong KKY, Liu X (2010) Silver nanoparticles—the real “silver bullet” in clinical medicine ? Medchemcomm 1:125–131

    Article  CAS  Google Scholar 

  58. Bastos V, Ferreira de Oliveira JMP, Brown D et al (2016) The influence of citrate or PEG coating on silver nanoparticle toxicity to a human keratinocyte cell line. Toxicol Lett 249:29–41

    Article  CAS  PubMed  Google Scholar 

  59. Sahariah P, Jensen KJ, Thygesen MB (2015) Antimicrobial peptide shows enhanced activity and reduced toxicity upon grafting to chitosan polymers. Chem Commun 51:5–8

    Article  Google Scholar 

  60. Martínez-Gutierrez F, Thi EP, Silverman JM et al (2012) Antibacterial activity, inflammatory response, coagulation and cytotoxicity effects of silver nanoparticles. Nanomed Nanotechnol Biol Med 8:328–336

    Article  Google Scholar 

  61. Zhou Y, Zhang T, Wang X et al (2015) Curcumin modulates macrophage polarization through the inhibition of the toll-like receptor 4 expression and its signaling pathways. Cell Physiol Biochem 36:631–641

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Swati Jaiswal acknowledges financial support as JRF (Junior Research Fellowship) and SRF (Senior Research Fellowship) from MHRD (Ministry of Human Resource and Development) Grant of Indian Institute of Technology Delhi (IITD), New Delhi. The work was partially funded by MeitY (Ministry of Electronics and Information Technology) and ICMR (Indian Council of Medical Research), Government of India to one of the authors (PM). We acknowledge TEM and SAED facilities of Physics Department, Indian Institute of Technology Delhi, New Delhi.

Author information

Authors and Affiliations

  1. Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology Delhi, Hauz Khas, New Delhi, India

    Swati Jaiswal & Prashant Mishra

Authors
  1. Swati Jaiswal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Prashant Mishra
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Prashant Mishra.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 1217 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jaiswal, S., Mishra, P. Antimicrobial and antibiofilm activity of curcumin-silver nanoparticles with improved stability and selective toxicity to bacteria over mammalian cells. Med Microbiol Immunol 207, 39–53 (2018). https://doi.org/10.1007/s00430-017-0525-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00430-017-0525-y

Keywords

Search

Navigation