Antifungal Nanotherapy: A Novel Approach to Combat Superficial Fungal Infections

  • Farnoush Asghari-Paskiabi
  • Zahra Jahanshiri
  • Masoomeh Shams-Ghahfarokhi
  • Mehdi Razzaghi-AbyanehEmail author


Superficial fungal infections (SFIs) affect up to 25% of population all over the world. Although dermatophytosis is the main SFIs with worldwide distribution, tinea versicolor caused by Malassezia species and Candida-related infections are also common. SFIs have diverse etiologic agents, which differ in pathogenesis and geographic distribution with increasing rate of resistant species to current antifungal therapy. Nowadays, the conventional antifungal therapy of SFIs using current antifungals of azoles, allylamines, and griseofulvin have some drawbacks like liver toxicity, skin problem, severe headaches and sometimes recurrences and drug–drug interactions especially in patients who are under drug treatment for other diseases. The problem is more complicated in immunocompromised patients who undergone systemic immunosuppressive therapies. On the other hand, low penetration of antifungal drugs in hard tissues of nail in onychomycoses caused by the dermatophytes and Candida species in local therapies and drug resistance in emerging causative species are considered as other important limitations of current antifungal therapy against SFIs. Novel formulations of antifungals or new devices that increase the chance of the delivery of the drug into the site of the infection seem necessary in order to enhance the drug efficiency. Recently, nanotechnology has contributed into this area and proposes great opportunities for more effective treatments of SFIs. In this chapter, we highlight current status of antifungal nanotherapy using advanced nanoformulations to combat SFIs and discuss in details their application in future medicine.


Nanotechnology Fungal infections Antifungal activity Nanocarriers Nanoparticles Dermatophytosis Candidiasis 



Clinical and Laboratory Standards Institute


Confocal Laser Scanning Microscopy


Fetal Bovine Serum


80% Inhibitory Concentration


Malt extract, Glucose, Yeast extract and Peptone








Poly Ethylene Glycol


Poly(Ethylene Oxide)


Propylene Glycol


Reactive Oxygen Species


Scanning Electron Microscope


X-ray diffraction


Yeast extract/Peptone/Dextrose


  1. Ahmad A, Wei Y, Syed F, Tahir K, Taj R, Khan A, Hameed M, Yuan Q (2016) Amphotericin B-conjugated biogenic silver nanoparticles as an innovative strategy for fungal infections. Microb Pathog 99:271–281PubMedCrossRefPubMedCentralGoogle Scholar
  2. Ameen M (2010) Epidemiology of superficial fungal infections. Clin Dermatol 28:197–201PubMedCrossRefPubMedCentralGoogle Scholar
  3. Asghari-Paskiabi F, Jahanshiri Z, Imani M, Shams-Ghahfarokhi M, Razzaghi-Abyaneh M (2016) In: Grumezescu AM (ed) Antifungal nanomaterials: synthesis, properties, and applications. Nanobiomaterials in antimicrobial therapy, vol 6. Elsevier, Oxford, pp 343–383Google Scholar
  4. Asghari-Paskiabi F, Imani M, Razzaghi-Abyaneh M, Rafii-Tabar H (2018) Fusarium oxysporum, a bio-factory for nano selenium compounds: synthesis and characterization. Sci Iran 25:1857–1863Google Scholar
  5. Asghari-Paskiabi F, Imani M, Rafii-Tabar H, Razzaghi-Abyaneh M (2019) Physicochemical properties, antifungal activity and cytotoxicity of selenium sulfide nanoparticles green synthesized by Saccharomyces cerevisiae. Biochem Biophys Res Commun 516:1078–1084PubMedCrossRefPubMedCentralGoogle Scholar
  6. Benson HAE (2006) Transfersomes for transdermal drug delivery. Expert Opin Drug Deliv 3:727–737PubMedCrossRefPubMedCentralGoogle Scholar
  7. Benson HAE (2009) Elastic liposomes for topical and transdermal drug delivery. Curr Drug Deliv 6:217–226PubMedCrossRefPubMedCentralGoogle Scholar
  8. Bhalaria MK, Naik S, Misra AN (2009) Ethosomes: a novel delivery system for antifungal drugs in the treatment of topical fungal diseases. Indian J Exp Biol 47:368–375PubMedPubMedCentralGoogle Scholar
  9. Blume A, Jansen M, Ghyczy M, Gareiss J (1993) Interaction of phospholipid liposomes with lipid model mixtures for stratum corneum lipids. Int J Pharm 99:219–228CrossRefGoogle Scholar
  10. Campani V, Biondi M, Laura M, Cilurzo F, Franzé S, Pitaro M, De Rosa G (2016) Nanocarriers to enhance the accumulation of vitamin K1 into the skin. Pharm Res 33:893–908PubMedCrossRefPubMedCentralGoogle Scholar
  11. Cevc G, Blume G (1992) Lipid vesicles penetrate into intact skin owing to the transdermal osmotic gradients and hydration force. Biochim Biophys Acta Biomembr 1104:226–232CrossRefGoogle Scholar
  12. Devi KP, Nisha SA, Sakthivel R, Pandian SK (2010) Eugenol (an essential oil of clove) acts as an antibacterial agent against Salmonella typhi by disrupting the cellular membrane. J Ethnopharmacol 130:107–115PubMedCrossRefPubMedCentralGoogle Scholar
  13. Dias MFRG, Quaresma-Santos M, Bernardes-Filho F, Amorim AGF, Schechtman RC, Azulay DR (2013) Update on therapy for superficial mycoses: review article part I. An Bras Dermatol 88:764–774PubMedPubMedCentralCrossRefGoogle Scholar
  14. Edwin B, Kannan I, Aarthi R, Sukumar RG, Prevathi RK, Shantha S (2017) Study on anti-fungal activity of silver nanoparticles obtained from Lawsonia inermis against Candida albicans and dermatophytes. Int J Adv Res Med Sci 1:19–22Google Scholar
  15. Elmoslemany RM, Abdallah O, El-Khordagui LK, Khalafallah NM (2012) Propylene glycol liposomes as a topical delivery system for miconazole nitrate: comparison with conventional liposomes. AAPS Pharm Sci Tech 13:723–731CrossRefGoogle Scholar
  16. Elsherif NI, Shamma RN, Abdelbary G (2017) Terbinafine hydrochloride trans-ungual delivery via nanovesicular systems: in vitro characterization and ex vivo evaluation. AAPS Pharm Sci Tech 18:551–562CrossRefGoogle Scholar
  17. Gholami-Shabani MA, Akbarzadeh A, Norouzian D, Amini A, Gholami-Shabani Z, Imani A, Chiani M, Riazi G, Shams-Ghahfarokhi M, Razzaghi-Abyaneh M (2014) Antimicrobial activity and physical characterization of silver nanoparticles green synthesized using nitrate reductase from Fusarium oxysporum. Appl Biochem Biotechnol 172:4084–4098PubMedCrossRefPubMedCentralGoogle Scholar
  18. Gholami-Shabani M, Imani A, Shams-Ghahfarokhi M, Gholami-Shabani Z, Pazooki A, Akbarzadeh A, Riazi G, Razzaghi-Abyaneh M (2016) Bioinspired synthesis, characterization and antifungal activity of enzyme-mediated gold nanoparticles using a fungal oxidoreductase. J Iran Chem Soc 13:2059–2068CrossRefGoogle Scholar
  19. Hamishehkar H, Rahimpour Y, Kouhsoltani M (2013) Niosomes as a propitious carrier for topical drug delivery. Expert Opin Drug Deliv 10:261–272PubMedCrossRefPubMedCentralGoogle Scholar
  20. Hartsel S, Bolard J (1996) Amphotericin B: new life for an old drug. Trends Pharmacol Sci 17:445–449PubMedCrossRefGoogle Scholar
  21. Havlickova B, Czaika V, Friedrich M (2008) Epidemiological trends in skin mycoses worldwide. Mycoses 51:2–15PubMedCrossRefGoogle Scholar
  22. Hay R (2017) Superficial fungal infections. Medicine 45:707–710CrossRefGoogle Scholar
  23. Hussain A, Singh S, Sharma D, Webster T, Shafaat K, Faruk A (2017) Elastic liposomes as novel carriers: recent advances in drug delivery. Int J Nanomedicine 12:5087PubMedPubMedCentralCrossRefGoogle Scholar
  24. Joshi PA, Bonde SR, Gaikwad SC, Gade AK, Abd-Elsalam K, Rai MK (2013) Comparative studies on synthesis of silver nanoparticles by Fusarium oxysporum and Macrophomina phaseolina and its efficacy against bacteria and Malassezia furfur. J Bionanosci 7:378–385CrossRefGoogle Scholar
  25. Kassem MAA, Esmat S, Bendas E, El-Komy M (2006) Efficacy of topical griseofulvin in treatment of tinea corporis. Mycoses 49:232–235PubMedCrossRefGoogle Scholar
  26. Kaushik N, Pujalte G, Reese S (2015) Superficial fungal infections. Primary Care Clin Office Pract 42:501–516CrossRefGoogle Scholar
  27. Kim K-J, Sung W, Moon S, Choi J, Kim JG, Lee DG (2008) Antifungal effect of silver nanoparticles on dermatophytes. J Microbiol Biotechnol 18:1482–1484PubMedGoogle Scholar
  28. Kim K-J, Sung W, Suh BK, Moon S, Choi J-S, Kim JG, Lee DG (2009) Antifungal activity and mode of action of silver nano-particles on Candida albicans. Biometals 22:235–242PubMedCrossRefGoogle Scholar
  29. Kumar R, Shukla S, Pandey A, Srivastava S, Dikshit A (2015) Copper oxide nanoparticles: an antidermatophytic agent for Trichophyton spp. Nanotechnol Rev 4:401–409Google Scholar
  30. Kumar L, Verma S, Singh K, Prasad DN, Jain AK (2016) Ethanol based vesicular carriers in transdermal drug delivery: nanoethosomes and transethosomes in focus. Nano World J 2:41–51Google Scholar
  31. Lee J, Kim KJ, Sung WS, Kim JG, Lee DG (2010) The silver nanoparticle (nano-Ag): a new model for antifungal agents. Silver nanoparticles. InTech, RijekaGoogle Scholar
  32. Li C, Wang X, Chen F, Zhang C, Zhi X, Wang K, Cui D (2013) The antifungal activity of graphene oxide-silver nanocomposites. Biomaterials 34:3882–3890PubMedCrossRefPubMedCentralGoogle Scholar
  33. Marcato PD, Durán M, Huber SC, Rai M, Melo PS, Alves OL, Duran N (2012) Biogenic silver nanoparticles and its antifungal activity as a new topical transungual drug. J Nano Res 20:99–107CrossRefGoogle Scholar
  34. Mofidfar M, Wang J, Long L, Hager C, Vareechon C, Pearlman E, Eric B, Ghannoum M, Wnek GE (2017) Polymeric nanofiber/antifungal formulations using a novel co-extrusion approach. AAPS Pharm Sci Tech 18:1917–1924CrossRefGoogle Scholar
  35. Mousavi SAA, Salari S, Hadizadeh S (2015) Evaluation of antifungal effect of silver nanoparticles against Microsporum canis, Trichophyton mentagrophytes and Microsporum gypseum. Iran J Biotechnol 13:38–43CrossRefGoogle Scholar
  36. Niemirowicz K, Bonita D, Tokajuk G, Głuszek K, Wilczewska AZ, Misztalewska I, Mystkowska J, Michalak G, Sodo A, Wątek M, Kiziewicz B, Góźdź S, Głuszek S, Bucki R (2016) Magnetic nanoparticles as a drug delivery system that enhance fungicidal activity of polyene antibiotics. Nanomed Nanotechnol Biol Med 12:2395–2404CrossRefGoogle Scholar
  37. Ouf SA, Mohamed AAH, El-Adly AA (2017) Enhancement of the antidermatophytic activity of silver nanoparticles by Q-switched Nd: YAG laser and monoclonal antibody conjugation. Med Mycol 55:495–506PubMedPubMedCentralGoogle Scholar
  38. Pandit J, Garg M, Jain NK (2014) Miconazole nitrate bearing ultraflexible liposomes for the treatment of fungal infection. J Liposome Res 24:163–169PubMedCrossRefGoogle Scholar
  39. Pannu J, McCarthy A, Martin A, Hamouda T, Ciotti S, Fothergill A, Sutcliffe J (2009) NB-002, a novel nanoemulsion with broad antifungal activity against dermatophytes, other filamentous fungi, and Candida albicans. Antimicrob Agents Chemother 53:3273–3279PubMedPubMedCentralCrossRefGoogle Scholar
  40. Paskiabi FA, Bonakdar S, Shokrgozar MA, Imani M, Jahanshiri Z, Shams-Ghahfarokhi M, Razzaghi-Abyaneh M (2017) Terbinafine-loaded wound dressing for chronic superficial fungal infections. Mater Sci Eng C 73:130–136CrossRefGoogle Scholar
  41. Pereira L, Dias N, Carvalho J, Fernandes S, Santos C, Lima N (2014) Synthesis, characterization and antifungal activity of chemically and fungal-produced silver nanoparticles against Trichophyton rubrum. J Appl Microbiol 117:1601–1613PubMedCrossRefPubMedCentralGoogle Scholar
  42. Rathna GS, Elavarasi A, Peninal S, Subramanian J, Mano G, Kalaiselvam M (2013) Extracellular biosynthesis of silver nanoparticles by endophytic fungus Aspergillus terreus and its anti-dermatophytic activity. Int J Pharmaceut Biol Arch 4:481–487Google Scholar
  43. Razzaghi-Abyaneh M, Shams-Ghahfarokhi M, Rai M (2015) Medical mycology: current trends and future prospects, 1st edn. CRC, Boca Raton, FLCrossRefGoogle Scholar
  44. Rónavári A, Igaz N, Gopisetty M, Szerencsés B, Kovács D, Papp C, Vágvölgyi C, Boros IM, Kónya Z, Kiricsi M, Pfeiffer I (2018) Biosynthesized silver and gold nanoparticles are potent antimycotics against opportunistic pathogenic yeasts and dermatophytes. Int J Nanomedicine 13:695–704PubMedPubMedCentralCrossRefGoogle Scholar
  45. Sadeghi G, Ebrahimi-Rad M, Mousavi SF, Shams-Ghahfarokhi M, Razzaghi-Abyaneh M (2018) Emergence of non-Candida albicans species: Epidemiology, phylogeny and fluconazole susceptibility profile. J Mycol Méd 28:51–58PubMedCrossRefPubMedCentralGoogle Scholar
  46. Salehi Z, Shams-Ghahfarokhi M, Razzaghi-Abyaneh M (2018) Antifungal drug susceptibility profile of clinically important dermatophytes and determination of point mutations in terbinafine-resistant isolate. Eur J Clin Microbiol Infect Dis 37:1841–1846PubMedCrossRefPubMedCentralGoogle Scholar
  47. Schwartz RA (2004) Superficial fungal infections. Lancet 364:1173–1182PubMedCrossRefPubMedCentralGoogle Scholar
  48. Scorzoni L, de Paula e Silva AC, Marcos CM, Assato PA, de Melo WCMA, de Oliveira HC, Costa-Orlandi CB, Mendes-Giannini MJS, Fusco-Almeida AM (2017) Antifungal therapy: new advances in the understanding and treatment of mycosis. Front Microbiol 8:36–59PubMedPubMedCentralCrossRefGoogle Scholar
  49. Seebacher C, Bouchara J-P, Mignon B (2008) Updates on the epidemiology of dermatophyte infections. Mycopathologia 166:335–352PubMedCrossRefPubMedCentralGoogle Scholar
  50. Semnani K, Shams-Ghahfarokhi M, Afrashi M, Fakhrali A, Semnani D (2018) Antifungal activity of eugenol loaded electrospun pan nanofiber mats against Candida albicans. Curr Drug Deliv 15:860–866PubMedCrossRefPubMedCentralGoogle Scholar
  51. Son KH, Kwon SY, Kim HP, Chang HW, Kang SS (1998) Constituents from Syzygium aromaticum Merr. et Perry. Nat Prod Sci 4:263–267Google Scholar
  52. Song CK, Balakrishnan P, Shim C-K, Chung S-J, Chong S, Kim D-D (2012) A novel vesicular carrier, transethosome, for enhanced skin delivery of voriconazole: characterization and in vitro/in vivo evaluation. Colloids Surf B Biointerfaces 92:299–304PubMedCrossRefPubMedCentralGoogle Scholar
  53. Sudhakar B, Ravi VJN, Ramana MKV (2014) Formulation, characterization and ex vivo studies of terbinafine hydrochloride liposomes for cutaneous delivery. Curr Drug Deliv 11:521–530PubMedCrossRefPubMedCentralGoogle Scholar
  54. Thakkar M (2016) Opportunities and challenges for niosomes as drug delivery systems. Curr Drug Deliv 13:1275–1289PubMedCrossRefPubMedCentralGoogle Scholar
  55. Tiwari N, Pandit R, Gaikwad S, Aniket G, Rai M (2016) Biosynthesis of zinc oxide nanoparticles by petals extract of Rosa indica L., its formulation as nail paint and evaluation of antifungal activity against fungi causing onychomycosis. IET Nanobiotechnol 11:205–211CrossRefGoogle Scholar
  56. Vandeputte P, Ferrari S, Coste TA (2012) Antifungal resistance and new strategies to control fungal infections. Int J Microbiol 2012:713687PubMedCrossRefPubMedCentralGoogle Scholar
  57. Verma P, Pathak K (2012) Nanosized ethanolic vesicles loaded with econazole nitrate for the treatment of deep fungal infections through topical gel formulation. Nanomed Nanotechnol Biol Med 8:489–496CrossRefGoogle Scholar
  58. Verma S, Utreja P (2018) Vesicular nanocarrier based treatment of skin fungal infections: Potential and emerging trends in nanoscale pharmacotherapy. Asian J Pharmaceut Sci 4:1–13Google Scholar
  59. Wypij M, Czarnecka J, Dahm H, Rai M, Golinska P (2017) Silver nanoparticles from Pilimelia columellifera subsp. pallida SL19 strain demonstrated antifungal activity against fungi causing superficial mycoses. J Basic Microbiol 57:793–800PubMedCrossRefPubMedCentralGoogle Scholar
  60. Zamani S, Sadeghi G, Yazdinia F, Moosa H, Pazooki A, Ghafarinia Z, Abbasi M, Shams-Ghahfarokhi M, Razzaghi-Abyaneh M (2016) Epidemiological trends of dermatophytosis in Tehran, Iran: a five-year retrospective study. J Mycol Méd 26:351–358PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Farnoush Asghari-Paskiabi
    • 1
  • Zahra Jahanshiri
    • 1
  • Masoomeh Shams-Ghahfarokhi
    • 2
  • Mehdi Razzaghi-Abyaneh
    • 1
    Email author
  1. 1.Department of MycologyPasteur Institute of IranTehranIran
  2. 2.Department of Mycology, Faculty of Medical SciencesTarbiat Modares UniversityTehranIran

Personalised recommendations