DOI QR코드

DOI QR Code

Gold Nanoparticles Conjugation Enhances Antiacanthamoebic Properties of Nystatin, Fluconazole and Amphotericin B

  • Anwar, Ayaz (Department of Biological Sciences, School of Science and Technology, Sunway University) ;
  • Siddiqui, Ruqaiyyah (Department of Biological Sciences, School of Science and Technology, Sunway University) ;
  • Shah, Muhammad Raza (International Center for Chemical and Biological Sciences, H.E.J. Research Institute of Chemistry, University of Karachi) ;
  • Khan, Naveed Ahmed (Department of Biological Sciences, School of Science and Technology, Sunway University)
  • Received : 2018.05.17
  • Accepted : 2018.11.01
  • Published : 2019.01.28

Abstract

Parasitic infections have remained a significant burden on human and animal health. In part, this is due to lack of clinically-approved, novel antimicrobials and a lack of interest by the pharmaceutical industry. An alternative approach is to modify existing clinically-approved drugs for efficient delivery formulations to ensure minimum inhibitory concentration is achieved at the target site. Nanotechnology offers the potential to enhance the therapeutic efficacy of drugs through modification of nanoparticles with ligands. Amphotericin B, nystatin, and fluconazole are clinically available drugs in the treatment of amoebal and fungal infections. These drugs were conjugated with gold nanoparticles. To characterize these gold-conjugated drug, atomic force microscopy, ultraviolet-visible spectrophotometry and Fourier transform infrared spectroscopy were performed. These drugs and their gold nanoconjugates were examined for antimicrobial activity against the protist pathogen, Acanthamoeba castellanii of the T4 genotype. Moreover, host cell cytotoxicity assays were accomplished. Cytotoxicity of these drugs and drug-conjugated gold nanoparticles was also determined by lactate dehydrogenase assay. Gold nanoparticles conjugation resulted in enhanced bioactivity of all three drugs with amphotericin B producing the most significant effects against Acanthamoeba castellanii (p < 0.05). In contrast, bare gold nanoparticles did not exhibit antimicrobial potency. Furthermore, amoebae treated with drugs-conjugated gold nanoparticles showed reduced cytotoxicity against HeLa cells. In this report, we demonstrated the use of nanotechnology to modify existing clinically-approved drugs and enhance their efficacy against pathogenic amoebae. Given the lack of development of novel drugs, this is a viable approach in the treatment of neglected diseases.

Keywords

References

  1. Li X, Robinson SM, Gupta A, Saha K, Jiang Z, Moyano DF, et al. 2014. Functional gold nanoparticles as potent antimicrobial agents against multi-drug-resistant bacteria. ACS Nano 8: 10682-10686. https://doi.org/10.1021/nn5042625
  2. Yang X, Yang J, Wang L, Ran B, Jia Y, Zhang L, et al. 2017. Pharmaceutical Intermediate-modified gold nanoparticles: against multidrug-resistant bacteria and wound-healing application via electrospun scaffold. ACS Nano 11: 5737-5745. https://doi.org/10.1021/acsnano.7b01240
  3. Maincent P, Le Verge R, Sado P, Couvreur P, Devissaguet J-P. 1986. Disposition kinetics and oral bioavailability of vincamine-loaded polyalkyl cyanoacrylate nanoparticles. J. Pharm. Sci. 75: 955-958. https://doi.org/10.1002/jps.2600751009
  4. Aqeel Y, Siddiqui R, Anwar A, Shah MR, Khan NA. 2016. Gold nanoparticle conjugation enhances the antiacanthamoebic effects of chlorhexidine. Antimicrob. Agents Chemother. 60: 1283-1288. https://doi.org/10.1128/AAC.01123-15
  5. Grace AN, Pandian K. 2007. Antibacterial efficacy of aminoglycosidic antibiotics protected gold nanoparticles-A brief study. Colloids Surfaces A: Physicochem. Eng. Aspects. 297: 63-70. https://doi.org/10.1016/j.colsurfa.2006.10.024
  6. Wilczewska AZ, Niemirowicz K, Markiewicz KH, Car H. 2012. Nanoparticles as drug delivery systems. Pharmacol. Rep. 64: 1020-1037. https://doi.org/10.1016/S1734-1140(12)70901-5
  7. Martinez A, Visvesvara G. 1991. Laboratory diagnosis of pathogenic free-living amoebas: Naegleria, Acanthamoeba, and Leptomyxid. Clin. Lab Med. 11: 861-872. https://doi.org/10.1016/S0272-2712(18)30524-9
  8. Marciano-Cabral F, Cabral G. 2003. Acanthamoeba spp. as agents of disease in humans. Clin. Microbiol. Rev. 16: 273-307. https://doi.org/10.1128/CMR.16.2.273-307.2003
  9. Khan NA. 2006. Acanthamoeba: biology and increasing importance in human health. FEMS Microbiol. Rev. 30: 564-595. https://doi.org/10.1111/j.1574-6976.2006.00023.x
  10. Seal D, Hay J, Kirkness C. 1995. Chlorhexidine or polyhexamethylene biguanide for Acanthamoeba keratitis. Lancet 345: 136. https://doi.org/10.1016/S0140-6736(95)90106-X
  11. Ishibashi Y, Matsumoto Y, Kabata T, Watanabe R, Hommura S, Yasuraoka K, et al. 1990. Oral itraconazole and topical miconazole with debridement for Acanthamoeba keratitis. Am. J. Ophthalmol. 109: 121-126. https://doi.org/10.1016/S0002-9394(14)75974-4
  12. Visvesvara GS, Moura H, Schuster FL. 2007. Pathogenic and opportunistic free-living amoebae: Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri, and Sappinia diploidea. FEMS Immunol. Med. Microbiol. 50: 1-26. https://doi.org/10.1111/j.1574-695X.2007.00232.x
  13. Girois S, Chapuis F, Decullier E, Revol B. 2005. Adverse effects of antifungal therapies in invasive fungal infections: review and meta-analysis. Eur. J. Clin. Microbiol. Infect. Dis. 24: 119-130. https://doi.org/10.1007/s10096-005-1281-2
  14. Martin-Navarro CM, Lopez-Arencibia A, Sifaoui I, Reyes-Batlle M, Valladares B, Martinez-Carretero E, et al. 2015. Statins and voriconazole induce programmed cell death in Acanthamoeba castellanii. Antimicrob. Agents Chemother. 59: 2817-2824. https://doi.org/10.1128/AAC.00066-15
  15. Thomson S, Rice CA, Zhang T, Edrada-Ebel R, Henriquez FL, Roberts CW. 2017. Characterisation of sterol biosynthesis and validation of $14{\alpha}$-demethylase as a drug target in Acanthamoeba. Sci. Rep. 7: 8247. https://doi.org/10.1038/s41598-017-07495-z
  16. Anwar A, Siddiqui R, Hussain MA, Ahmed D, Shah MR, Khan NA. 2018. Silver nanoparticle conjugation affects antiacanthamoebic activities of amphotericin B, nystatin, and fluconazole. Parasitol. Res. 117: 265-271. https://doi.org/10.1007/s00436-017-5701-x
  17. Anwar A, Shah MR, Muhammad SP, Afridi S, Ali K. 2016. Thiopyridinium capped silver nanoparticle based supramolecular recognition of Cu (I) in real samples and T-lymphocytes. New J. Chem. 40: 6480-6486. https://doi.org/10.1039/C5NJ03609G
  18. Sissons J, Alsam S, Stins M, Rivas AO, Morales JL, Faull J, et al. 2006. Use of in vitro assays to determine effects of human serum on biological characteristics of Acanthamoeba castellanii. J. Clin. Microbiol. 44: 2595-2600. https://doi.org/10.1128/JCM.00144-06
  19. Khan NA, Siddiqui R. 2009. Acanthamoeba affects the integrity of human brain microvascular endothelial cells and degrades the tight junction proteins. Int. J. Parasitol. 39: 1611-1616. https://doi.org/10.1016/j.ijpara.2009.06.004
  20. Ali SM, Siddiqui R, Ong SK, Shah MR, Anwar A, Heard PJ, et al. 2017. Identification and characterization of antibacterial compound (s) of cockroaches (Periplaneta americana). Appl. Microbiol. Biotechnol. 101: 253-286. https://doi.org/10.1007/s00253-016-7872-2
  21. Radwan MA, AlQuadeib BT, Siller L, Wright MC, Horrocks B. 2017. Oral administration of amphotericin B nanoparticles: antifungal activity, bioavailability and toxicity in rats. Drug Deliv. 24: 40-50. https://doi.org/10.1080/10717544.2016.1228715
  22. Rodino S, Butu M, Negoescu C, Caunii A, Cristina R, Butnariu M. 2014. Spectrophotometric method for quantitative determination of nystatin antifungal agent in pharmaceutical formulations. Digest J. Nanomater. Biostruc. 9: 1215-1222.
  23. Singh A, Sharma P, Majumdar D. 2011. Development and validation of different UV-spectrophotometric methods for the estimation of fluconazole in bulk and in solid dosage form. Indian J. Chem. Technol. 18: 357-362.
  24. Suri SS, Fenniri H, Singh B. 2007. Nanotechnology-based drug delivery systems. J. Occup. Med. Toxicol. 2: 16. https://doi.org/10.1186/1745-6673-2-16
  25. Walsh M D, Hanna S K, S en J , Rawal S, C abral CB , Yurkovetskiy AV, et al. 2012. Pharmacokinetics and antitumor efficacy of XMT-1001, a novel, polymeric topoisomerase I inhibitor, in mice bearing HT-29 human colon carcinoma xenografts. Clin. Cancer Res. 18: 2591-2602. https://doi.org/10.1158/1078-0432.CCR-11-1554
  26. Zazo H, Colino CI, Lanao JM. 2016. Current applications of nanoparticles in infectious diseases. J. Control Release. 224: 86-102. https://doi.org/10.1016/j.jconrel.2016.01.008
  27. Ahmed D, Anwar A, Khan AK, Ahmed A, Shah MR, Khan NA. 2017. Size selectivity in antibiofilm activity of 3-(diphenylphosphino) propanoic acid coated gold nanomaterials against Gram-positive Staphylococcus aureus and Streptococcus mutans. AMB Express 7: 210. https://doi.org/10.1186/s13568-017-0515-x
  28. Dakal TC, Kumar A, Majumdar RS, Yadav V. 2016. Mechanistic basis of antimicrobial actions of silver nanoparticles. Front Microbiol. 7: 1831.
  29. Pal S, Tak YK, Song JM. 2007. Does the antibacterial activity of silver nanoparticles depend on the shape of the nanoparticle? A study of the gram-negative bacterium Escherichia coli. Appl. Environ. Microbiol. 73: 1712-1720. https://doi.org/10.1128/AEM.02218-06
  30. Zhao G, Stevens SE. 1998. Multiple parameters for the comprehensive evaluation of the susceptibility of Escherichia coli to the silver ion. Biometals 11: 27-32. https://doi.org/10.1023/A:1009253223055

Cited by

  1. Antidiabetic Drugs and Their Nanoconjugates Repurposed as Novel Antimicrobial Agents against Acanthamoeba castellanii vol.29, pp.5, 2019, https://doi.org/10.4014/jmb.1903.03009
  2. Gold nanoparticles in chemo-, immuno-, and combined therapy: review [Invited] vol.10, pp.7, 2019, https://doi.org/10.1364/boe.10.003152
  3. Acanthamoeba in Southeast Asia - Overview and Challenges vol.57, pp.4, 2019, https://doi.org/10.3347/kjp.2019.57.4.341
  4. Gut bacteria of Cuora amboinensis (turtle) produce broad-spectrum antibacterial molecules vol.9, pp.1, 2019, https://doi.org/10.1038/s41598-019-52738-w
  5. Repositioning of Guanabenz in Conjugation with Gold and Silver Nanoparticles against Pathogenic Amoebae Acanthamoeba castellanii and Naegleria fowleri vol.5, pp.12, 2019, https://doi.org/10.1021/acsinfecdis.9b00263
  6. Antibacterial Properties of Functionalized Gold Nanoparticles and Their Application in Oral Biology vol.2020, 2020, https://doi.org/10.1155/2020/5616379
  7. Silver Nanoparticles as a Novel Potential Preventive Agent against Acanthamoeba Keratitis vol.9, pp.5, 2019, https://doi.org/10.3390/pathogens9050350
  8. Synthesis of Thiol Derivatives of Biological Active Compounds for Nanotechnology Application vol.25, pp.15, 2020, https://doi.org/10.3390/molecules25153470
  9. Repurposing of Drugs Is a Viable Approach to Develop Therapeutic Strategies against Central Nervous System Related Pathogenic Amoebae vol.11, pp.16, 2020, https://doi.org/10.1021/acschemneuro.9b00613
  10. Metronidazole conjugated magnetic nanoparticles loaded with amphotericin B exhibited potent effects against pathogenic Acanthamoeba castellanii belonging to the T4 genotype vol.10, pp.1, 2019, https://doi.org/10.1186/s13568-020-01061-z
  11. Rod-shaped gold nanoparticles exert potent candidacidal activity and decrease the adhesion of fungal cells vol.15, pp.28, 2019, https://doi.org/10.2217/nnm-2020-0324
  12. Toxicity of gold nanoparticles (AuNPs): A review vol.26, 2019, https://doi.org/10.1016/j.bbrep.2021.100991
  13. Acanthamoeba Keratitis: an update on amebicidal and cysticidal drug screening methodologies and potential treatment with azole drugs vol.19, pp.11, 2019, https://doi.org/10.1080/14787210.2021.1924673