Abstract
The ineffectiveness of azole drugs in treating Vulvovaginal Candidiasis (VVC) and Recurrent Vulvovaginal Candidiasis (RVVC) due to antifungal resistance of non-albicans Candida has led to the investigation of inorganic nanoparticles with biological activity. Silver nanoparticles (AgNPs) are important in nanomedicine and have been used in various products and technologies. This study aimed to develop a vaginal cream and assess its in vitro antimicrobial activity against Candida parapsilosis strains, specifically focusing on the synergy between AgNPs and miconazole. AgNPs were synthesized using glucose as a reducing agent and sodium dodecyl sulfate (SDS) as a stabilizer in varying amounts (0.50, 0.25, and 0.10 g). The AgNPs were characterized using UV–Visible (UV–Vis) and Fourier-Transform Infrared (FT-IR) spectroscopies, X-Ray Diffraction (XRD), Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), and Energy Dispersive X-Ray Analysis (EDX). Fifty strains of Candida parapsilosis were used to evaluate the synergistic activity. AgNPs synthesized with 0.5 g SDS had an average size of 77.58 nm and a zeta potential of −49.2 mV, while AgNPs with 0.25 g showed 91.22 nm and −47.2 mV, respectively. AgNPs stabilized with 0.1 g of SDS were not effective. When combined with miconazole, AgNPs exhibited significant antifungal activity, resulting in an average increase of 80% in inhibition zones. The cream developed in this study, containing half the miconazole concentration of commercially available medication, demonstrated larger inhibition zones compared to the commercial samples.
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs13205-023-03776-9/MediaObjects/13205_2023_3776_Fig1_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs13205-023-03776-9/MediaObjects/13205_2023_3776_Fig2_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs13205-023-03776-9/MediaObjects/13205_2023_3776_Fig3_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs13205-023-03776-9/MediaObjects/13205_2023_3776_Fig4_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs13205-023-03776-9/MediaObjects/13205_2023_3776_Fig5_HTML.png)
Similar content being viewed by others
Data availability
Not applicable.
References
Al-Bahrani RM, Majeed SMA, Owaid MN, Mohammed AB, Rheem DAJAPS (2018) Phyto-fabrication, characteristics and anticandidal effects of silver nanoparticles from leaves of Ziziphus mauritiana Lam. ACTA Pharm Sci 56(3):85
AlJindan R, AlEraky DM (2022) Silver nanoparticles: a promising antifungal agent against the growth and biofilm formation of the emergent Candida auris. J Fungi (basel) 8(7):744. https://doi.org/10.3390/jof8070744
Alula MT, Karamchand L, Hendricks NR, Blackburn JM (2018) Citrate-capped silver nanoparticles as a probe for sensitive and selective colorimetric and spectrophotometric sensing of creatinine in human urine. Anal Chim Acta 1007:40–49. https://doi.org/10.1016/j.aca.2017.12.016
Bélteky P, Rónavári A, Zakupszky D, Boka E, Igaz N, Szerencsés B, Pfeiffer I, Vágvölgyi C, Kiricsi M, Kónya Z (2021) Are smaller nanoparticles always better? Understanding the biological effect of size-dependent silver nanoparticle aggregation under biorelevant conditions. Int J Nanomed 16:3021–3040. https://doi.org/10.2147/IJN.S304138
Chandrasekharan S, Chinnasamy G, Bhatnagar S (2022) Sustainable phyto-fabrication of silver nanoparticles using Gmelina arborea exhibit antimicrobial and biofilm inhibition activity. Sci Rep 12(1):156. https://doi.org/10.1038/s41598-021-04025-w
Chudobova D, Nejdl L, Gumulec J, Krystofova O, Rodrigo MA, Kynicky J, Ruttkay-Nedecky B, Kopel P, Babula P, Adam V, Kizek R (2013) Complexes of silver(I) ions and silver phosphate nanoparticles with hyaluronic acid and/or chitosan as promising antimicrobial agents for vascular grafts. Int J Mol Sci 14(7):13592–13614. https://doi.org/10.3390/ijms140713592
Cianci A, Cicinelli E, Colacurci N, De Leo V, Perino A, Pino A, Bartolo E, Randazzo C, Esposito G, Chiaffarino F (2020) Diagnosis and treatment of vulvovaginal candidiasis: a practical approach. Ital J Gynaecol Obstetr 32(4):261–268
Cunha FA, Cunha M, da Frota SM, Mallmann EJJ, Freire TM, Costa LS, Paula AJ, Menezes EA, Fechine PBA (2018) Biogenic synthesis of multifunctional silver nanoparticles from Rhodotorula glutinis and Rhodotorula mucilaginosa: antifungal, catalytic and cytotoxicity activities. World J Microbiol Biotechnol 34(9):127. https://doi.org/10.1007/s11274-018-2514-8
da Frota S, Cunha F, Cunha MR, Menezes EJ (2018) synergistic effect of polyene antifungals and silver nanoparticles against Candida parapsilosis. J Antibiot Res 2(1):104
Devi LS, Joshi SR (2012) Antimicrobial and synergistic effects of silver nanoparticles synthesized using soil fungi of high altitudes of eastern Himalaya. Mycobiology 40(1):27–34. https://doi.org/10.5941/MYCO.2012.40.1.027
Dhasarathan P, AlSalhi MS, Devanesan S, Subbiah J, Ranjitsingh AJA, Binsalah M, Alfuraydi AA (2021) Drug resistance in Candida albicans isolates and related changes in the structural domain of Mdr1 protein. J Infect Public Health 14(12):1848–1853. https://doi.org/10.1016/j.jiph.2021.11.002
Farr A, Effendy I, Frey Tirri B, Hof H, Mayser P, Petricevic L, Ruhnke M, Schaller M, Schaefer APA, Sustr V, Willinger B, Mendling W (2021) Guideline: vulvovaginal candidosis (AWMF 015/072, level S2k). Mycoses 64(6):583–602. https://doi.org/10.1111/myc.13248
Gordienko MG, Palchikova VV, Kalenov SV, Belov AA, Lyasnikova VN, Poberezhniy DY, Chibisova AV, Sorokin VV, Skladnev DA (2019) Antimicrobial activity of silver salt and silver nanoparticles in different forms against microorganisms of different taxonomic groups. J Hazard Mater 378:120754. https://doi.org/10.1016/j.jhazmat.2019.120754
Guerra JD, Sandoval G, Avalos-Borja M, Pestryakov A, Garibo D, Susarrey-Arce A, Bogdanchikova N (2020) Selective antifungal activity of silver nanoparticles: a comparative study between Candida tropicalis and Saccharomyces boulardii. Colloid Interface Sci Commun 37:100280. https://doi.org/10.1016/j.colcom.2020.100280
Hamouda RA, Abd El-Mongy M, Eid KF (2019) Comparative study between two red algae for biosynthesis silver nanoparticles capping by SDS: insights of characterization and antibacterial activity. Microb Pathog 129:224–232. https://doi.org/10.1016/j.micpath.2019.02.016
Hashemi Z, Mizwari ZM, Mohammadi-Aghdam S, Mortazavi-Derazkola S, Ali Ebrahimzadeh M (2022) Sustainable green synthesis of silver nanoparticles using Sambucus ebulus phenolic extract (AgNPs@SEE): optimization and assessment of photocatalytic degradation of methyl orange and their in vitro antibacterial and anticancer activity. Arab J Chem 15(1):103525. https://doi.org/10.1016/j.arabjc.2021.103525
Jian Y, Chen X, Ahmed T, Shang Q, Zhang S, Ma Z, Yin Y (2022) Toxicity and action mechanisms of silver nanoparticles against the mycotoxin-producing fungus Fusarium graminearum. J Adv Res 38:1–12. https://doi.org/10.1016/j.jare.2021.09.006
Johnson MD (2021) Antifungals in clinical use and the pipeline. Infect Dis Clin North Am 35(2):341–371. https://doi.org/10.1016/j.idc.2021.03.005
Kora AJ, Manjusha R, Arunachalam J (2009) Superior bactericidal activity of SDS capped silver nanoparticles: synthesis and characterization. Mater Sci Eng C 29(7):2104–2109. https://doi.org/10.1016/j.msec.2009.04.010
Kumar CG, Poornachandra Y (2015) Biodirected synthesis of Miconazole-conjugated bacterial silver nanoparticles and their application as antifungal agents and drug delivery vehicles. Colloids Surf B 125:110–119. https://doi.org/10.1016/j.colsurfb.2014.11.025
Kumar CG, Mamidyala SK, Reddy MN, Reddy BVS (2012) Silver glyconanoparticles functionalized with sugars of sweet sorghum syrup as an antimicrobial agent. Process Biochem 47(10):1488–1495. https://doi.org/10.1016/j.procbio.2012.05.023
Lírio J, Giraldo PC, Sarmento AC, Costa APF, Cobucci RN, Saconato H, Eleutério Júnior J, Gonçalves AK (2022) Antifungal (oral and vaginal) therapy for recurrent vulvovaginal candidiasis: a systematic review and meta-analysis. Rev Assoc Med Brasil (1992) 68(2):261–267. https://doi.org/10.1590/1806-9282.20210916
Mare AD, Man A, Ciurea CN, Toma F, Cighir A, Mareș M, Berța L, Tanase C (2021) Silver nanoparticles biosynthesized with spruce bark extract—a molecular aggregate with antifungal activity against Candida species. Antibiotics 10(10):1261
Mehta SK, Chaudhary S, Gradzielski M (2010) Time dependence of nucleation and growth of silver nanoparticles generated by sugar reduction in micellar media. J Colloid Interface Sci 343(2):447–453. https://doi.org/10.1016/j.jcis.2009.11.053
Menezes EA, Vasconcelos Júnior AAd, Cunha FA, Cunha MCdSO, Braz BHL, Capelo LG, Silva CLF (2012) Molecular identification and antifungal susceptibility of Candida parapsilosis isolates in Ceará, Brazil. J Bras Patol Med Lab 48:415–420
Mondal AH, Yadav D, Ali A, Khan N, Jin JO, Haq QMR (2020) Anti-bacterial and anti-candidal activity of silver nanoparticles biosynthesized using Citrobacter spp. MS5 culture supernatant. Biomolecules 10(6):944. https://doi.org/10.3390/biom10060944
Moshfeghy Z, Tahari S, Janghorban R, Najib FS, Mani A, Sayadi M (2020) Association of sexual function and psychological symptoms including depression, anxiety and stress in women with recurrent vulvovaginal candidiasis. J Turk German Gynecol Assoc 21(2):90–96. https://doi.org/10.4274/jtgga.galenos.2019.2019.0077
Panáček A, Kolář M, Večeřová R, Prucek R, Soukupová J, Kryštof V, Hamal P, Zbořil R, Kvítek L (2009) Antifungal activity of silver nanoparticles against Candida spp. Biomaterials 30(31):6333–6340. https://doi.org/10.1016/j.biomaterials.2009.07.065
Parsapour H, Masoumi SZ, Shayan A, Moradkhani S, Ghiasian SA, Rashidi MK (2021) Comparison of the effects of nika vaginal cream with clotrimazole cream on vaginal candidiasis symptoms: A randomized single-blind clinical trial. Iran J Nurs Midwifery Res 26(6):521–525. https://doi.org/10.4103/ijnmr.IJNMR_82_20
Patil MU, Rajput AP, Belgamwar VS, Chalikwar SS (2022) Development and characterization of amphotericin B nanoemulsion-loaded mucoadhesive gel for treatment of vulvovaginal candidiasis. Heliyon 8(11):e11489. https://doi.org/10.1016/j.heliyon.2022.e11489
Radhakrishnan VS, Reddy Mudiam MK, Kumar M, Dwivedi SP, Singh SP, Prasad T (2018) Silver nanoparticles induced alterations in multiple cellular targets, which are critical for drug susceptibilities and pathogenicity in fungal pathogen (Candida albicans). Int J Nanomedicine 13:2647–2663. https://doi.org/10.2147/ijn.S150648
Rezaei H, Rahimpour E, Khoubnasabjafari M, Jouyban-Gharamaleki V, Jouyban A (2020) A colorimetric nanoprobe based on dynamic aggregation of SDS-capped silver nanoparticles for tobramycin determination in exhaled breath condensate. Microchim Acta 187(3):186. https://doi.org/10.1007/s00604-020-4162-6
Rosati D, Bruno M, Jaeger M, Ten Oever J, Netea MG (2020) Recurrent vulvovaginal candidiasis: an immunological perspective. Microorganisms 8(2):144. https://doi.org/10.3390/microorganisms8020144
Salah S, Awad GEA, Makhlouf AIA (2018) Improved vaginal retention and enhanced antifungal activity of miconazole microsponges gel: formulation development and in vivo therapeutic efficacy in rats. Eur J Pharm Sci 114:255–266. https://doi.org/10.1016/j.ejps.2017.12.023
Sarkar M, Denrah S, Das M, Das M (2021) Statistical optimization of bio-mediated silver nanoparticles synthesis for use in catalytic degradation of some azo dyes. Chem Phys Impact 3:100053. https://doi.org/10.1016/j.chphi.2021.100053
Singh M, Kumar M, Kalaivani R, Manikandan S, Kumaraguru AK (2013) Metallic silver nanoparticle: a therapeutic agent in combination with antifungal drug against human fungal pathogen. Bioprocess Biosyst Eng 36(4):407–415. https://doi.org/10.1007/s00449-012-0797-y
Sinha T, Gude V, Rao NVS (2012) Synthesis of silver nanoparticles using sodium dodecylsulphate. Adv Sci Eng Med 4(5):381–387. https://doi.org/10.1166/asem.2012.1195
Sobel JD, Nyirjesy P (2021) Oteseconazole: an advance in treatment of recurrent vulvovaginal candidiasis. Future Microbiol 16(18):1453–1461. https://doi.org/10.2217/fmb-2021-0173
Soliman AM, Abdel-Latif W, Shehata IH, Fouda A, Abdo AM, Ahmed YM (2021) Green approach to overcome the resistance pattern of Candida spp. using biosynthesized silver nanoparticles fabricated by Penicillium chrysogenum F9. Biol Trace Elem Res 199(2):800–811. https://doi.org/10.1007/s12011-020-02188-7
Swensson B, Ek M, Gray DG (2018) In situ preparation of silver nanoparticles in paper by reduction with alkaline glucose solutions. ACS Omega 3(8):9449–9452. https://doi.org/10.1021/acsomega.8b01199
Szerencsés B, Igaz N, Tóbiás Á, Prucsi Z, Rónavári A, Bélteky P, Madarász D, Papp C, Makra I, Vágvölgyi C, Kónya Z, Pfeiffer I, Kiricsi M (2020) Size-dependent activity of silver nanoparticles on the morphological switch and biofilm formation of opportunistic pathogenic yeasts. BMC Microbiol 20(1):176. https://doi.org/10.1186/s12866-020-01858-9
Tauseef A, Hisam F, Hussain T, Caruso A, Hussain K, Châtel A, Chénais B (2022) Nanomicrobiology: emerging trends in microbial synthesis of nanomaterials and their applications. J Cluster Sci. https://doi.org/10.1007/s10876-022-02256-z
Tayah DY, Eid AM (2023) Development of miconazole nitrate nanoparticles loaded in nanoemulgel to improve its antifungal activity. Saudi Pharm J 31(4):526–534. https://doi.org/10.1016/j.jsps.2023.02.005
Tóth R, Nosek J, Mora-Montes HM, Gabaldon T, Bliss JM, Nosanchuk JD, Turner SA, Butler G, Vágvölgyi C, Gácser A (2019) Candida parapsilosis: from genes to the bedside. Clin Microbiol Rev. https://doi.org/10.1128/cmr.00111-18
Vazquez-Muñoz R, Avalos-Borja M, Castro-Longoria E (2014) Ultrastructural analysis of Candida albicans when exposed to silver nanoparticles. PLoS ONE 9(10):e108876. https://doi.org/10.1371/journal.pone.0108876
Wei S, Wang Y, Tang Z, Hu J, Su R, Lin J, Zhou T, Guo H, Wang N, Xu R (2020) A size-controlled green synthesis of silver nanoparticles by using the berry extract of Sea Buckthorn and their biological activities. New J Chem 44(22):9304–9312. https://doi.org/10.1039/D0NJ01335H
Willems HME, Ahmed SS, Liu J, Xu Z, Peters BM (2020) Vulvovaginal candidiasis: a current understanding and burning questions. J Fungi (basel) 6(1):27. https://doi.org/10.3390/jof6010027
Acknowledgements
The authors thank Central Analítica-UFC/CT-INFRA/MCTI-SISNANO/Pró-Equipamentos for providing the SEM experiments and X-ray Diffraction Laboratory (LRX-UFC). This work was partially supported by NanoSaude: E-26/010.000981/2019, UEZO: E-26/010.002362/2019; Temáticos: E-26/211.269/2021, Infraestrutura and Pesquisa na UEZO, UERJ: E-26//211.207/2021, Bolsa de Pós-Doutorado Senior (PDS): E-26/202.320/2021 and CNPq (Bolsa de Produtividade 1C: 308452/2022-4 and 1B: 301069/2018-2). This work was also supported by CAPES (Finance Code 001-PROEX 23038.000509/2020-82) and Funcap (PNE-0112-00048.01.00/16).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors have no relevant financial or non-financial interests to disclose.
Ethical approval
This study did not involve the use of any human or animal model.
Informed consent
Not applicable.
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
Maciel, A.A.M., Cunha, F.A., Freire, T.M. et al. Development and evaluation of an anti-candida cream based on silver nanoparticles. 3 Biotech 13, 352 (2023). https://doi.org/10.1007/s13205-023-03776-9
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s13205-023-03776-9