In-Vitro Antifungal Activity of Nano Encapsulated Caprylic Acid and EFG1 Gene Expression Profile in Candida albicans

Document Type : Original Research

Authors
R. Zarimeidani 1
S. Roudbar mohammadi‎ 1
M. Roudbary 2
F. Nikoomanesh 3
P. Aslani 4
S. Yaalimadad 5
1 Department of Mycology, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran
2 Department of Parasitology and Mycology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
3 Infectious Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
4 Department of Parasitology and Mycology, Faculty of Medicine, Aja University of Medical Sciences
5 Department of Mycology, Faculty of Medical Science, Tarbiat Modares University, Tehran,Iran
10.52547/iem.7.3.229
Abstract
Backgrounds: Due to the emergence of multidrug-resistant Candida species, the discovery of new antifungal agents with minimum side effects is essential. The aim of this study was to investigate the antifungal activity of caprylic acid and nano-encapsulated caprylic acid against C. albicans as well as their effect on the expression of EFG1 gene.

Materials & Methods: In this laboratory trial study, the minimum inhibitory concentration (MIC) of caprylic acid and nano-encapsulated caprylic acid against C. albicans was evaluated at various concentrations (400-625 and 1.3-50 μL/mL, respectively). Real time-PCR was performed to assess the expression level of EFG1 gene. Cytotoxicity effect of caprylic acid and nano-encapsulated caprylic acid was evaluated on SW480 cell line using MTT test.

Findings: Antifungal activity findings displayed that MIC90 and MIC50 values of caprylic acid were 500 and 450 μg/mL, respectively, whereas MIC90 and MIC50 values of nano-encapsulated caprylic acid were 6.2 and 3.1 μg/mL, respectively. The expression of EFG1 gene significantly decreased in the groups treated with caprylic acid and nano-encapsulated caprylic acid compared to the control group. According to the cytotoxicity evaluation findings, the viability of cells treated with caprylic acid was significantly higher than that of cells exposed to nano-encapsulated caprylic acid.

Conclusions: According to the obtained results, nano-encapsulated caprylic acid successfully inhibited C. albicans growth at a lower concentration compared to caprylic acid. Overall, it was found that nano-encapsulated caprylic acid is a promising antifungal agent against Candida species; however, further studies are needed to be performed about nano-encapsulation of caprylic acid.

Keywords

Subjects

1. Khan MSA, Ahmad I, Aqil F, Owais M, Shahid M, Musarrat J. Virulence and pathogenicity of fungal pathogens with special reference to Candida albicans. Combating fungal infections: Springer; 2010. p. 21-45.
2. Cleveland AA, Harrison,L.H.,Farley,M.M.,Hollick,R.,Stein,B., Chiller, T.M.,etal. Decliningincidenceofcandidemiaandtheshifting epidemiologyof Candida resistancein two US metropolitanareas. PLoS ONE 2015;10:e0120452.
3. Klingspor L, Tortorano,A.M.,Peman,J.,Willinger,B.,Hamal,P.,Sendid,B., etal. Invasive Candida infections in surgical patients inintensive care units: aprospective. ClinMicrobiol Infect. 2015.
4. Finkel JS, Mitchell AP. Genetic control of Candida albicans biofilm development. Nature Reviews Microbiology. 2011;9(2):109-18.
5. Stanley NR, Lazazzera BA. Environmental signals and regulatory pathways that influence biofilm formation. Molecular microbiology. 2004;52(4):917-24.
6. Mitchell SGaaP. Mucosal biofilm of Candida albicans. Curent opinion in microbiology. 2011(14):380-5.
7. Donlan RM, Costerton JW. Biofilms: survival mechanisms of clinically relevant microorganisms. Clinical microbiology reviews. 2002;15(2):167-93.
8. Srikantha T, Tsai, L.K., Daniels, K. and Soll, D.R. EFG1 null mutants of Candida albicans switch but cannot express the complete phenotype of white-phase budding cells. J Bacteriol. 2000(182):1580-91.
9. Sohn K, Urban, C., Brunner, H., Rupp, S. EFG1 is a major regulator of cell wall dynamics in candida albicans as revealed by DNA microarrays. Molecular Microbiol. 2003;1(47):89-102.
10. Nadeem SG, Shafiq, A., Shazia, T., Yasmeen, Anjum, H., Shahana, U. Effect of growth media, pH and temperature on yeast to hyphal transition in Candida albicans. Open J medical Microbiol. 2013(3):185-92.
11. Guinea J, Sánchez-Somolinos M,Cuevas O, Peláez T ,and Bouza E. Fluconazoleresistancemechanismsin Candidakrusei: thecontribution ofefflux-pumps. MedMycol. 2006(44):575-8.
12. Nuzhat T VG. Antifungal investigations on plant essential oils. Internat J Pharm Pharmaceut Sci. 2014(5):19-28.
13. Walters D, Raynor L, Mitchell A, Walker R, Walker K. Antifungal activities of four fatty acids against plant pathogenic fungi. Mycopathologia. 2004;157(1):87-90.
14. Thibane VS KJ, Ells R, Van Wyk PWJ, Pohl CH. Effect of marine polyunsaturated fatty acids on biofilm formation of C. albicans and C. dubliniensis. Marine Drugs. 2010(8):2597-604.
15. Murzyn A KA, Stefanowicz P, Dziadkowiec D, Łukaszewicz M. . . 2010;. Capric acid secreted by S. boulardii inhibits C. albicans filamentous growth, adhesion and biofilm formation. PLos ONE. 2010(5:e12050).
16. Carballeira N. New advances in fatty acids as antimalarial, antimycobacterial and antifungal agents. Progress in lipid research. 2008;47(1):50-61.
17. Traul KA, Driedger A, Ingle DL, Nakhasi D. Review of the toxicologic properties of medium-chain triglycerides. Food Chem Toxicol. 2000; 38(1); P 79-98.
18. Kumari. A Y, S. K., Yadav, S. C. Biodegradable polymeric nanoparticles based drug delivery systems. Colloids and Surfaces Biointerfaces. 2010;75:1-18.
19. Nahar M DT, Murugesan S, Asthana A, Mishra D, Rajkumar V, Tare M, Saraf S, Jain NK. Functional polymeric nanoparticles: an efficient and promising tool for active delivery of bioactives. Crit Rev Ther Drug Carrier Syst. 2006;4(23):259-318.
20. Nikoomanesh F, Roudbarmohammadi S, Khoobi M, Haghighi F, Roudbary M. Design and synthesis of mucoadhesive nanogel containing farnesol: investigation of the effect on HWP1, SAP6 and Rim101 genes expression of Candida albicans in vitro. Artificial cells, nanomedicine, and biotechnology. 2019;47(1):64-72.
21. Nikoomanesh F, Bashardoust B. Effect of Farnesol on Responsive Gene Expressions in Hyphal‎ Morphogenesis Transformation of Candida albicans. Infection Epidemiology and Microbiology. 2018;4(2):73-7.
22. Maryam Roudbary SR, Bita Bakhshi, Zahra Farhadi and Fatemeh Nikoomanesh. Identification of Candida species isolated form Iranian women eith vaginal candidasis by PCR-RFLP method. European journal of experimental biology. 2013;3(6):365-9.
23. Trewyn BG, Slowing II, Giri S, Chen H-T, Lin VS-Y. Synthesis and functionalization of a mesoporous silica nanoparticle based on the sol–gel process and applications in controlled release. Accounts of chemical research. 2007;40(9):846-53.
24. Chinatangkul N, Limmatvapirat C, Nunthanid J, Luangtana-Anan M, Sriamornsak P, Limmatvapirat S. Design and characterization of monolaurin loaded electrospun shellac nanofibers with antimicrobial activity. Asian journal of pharmaceutical sciences. 2018;13(5):459-71.
25. Zhang H, Zhai Y, Wang J, Zhai G. New progress and prospects: The application of nanogel in drug delivery. Materials Science and Engineering: C. 2016;60:560-8.
26. Avis TJ, Bélanger RR. Specificity and Mode of Action of the Antifungal Fatty Acid cis-9-Heptadecenoic Acid Produced byPseudozyma flocculosa. Applied and environmental microbiology. 2001;67(2):956-60.
27. Bergsson G, Arnfinnsson J, Steingrı́msson Ó, Thormar H. In vitro killing of Candida albicans by fatty acids and monoglycerides. Antimicrobial agents and chemotherapy. 2001;45(11):3209-12.
28. Takahashi M, Inoue S, Hayama K, Ninomiya K, Abe S. Inhibition of Candida Mycelia Growth by a Medium Chain Fatty Acids, Capric Acid in Vitoro and its Therapeutic Efficacy in Murine Oral Candidiasis. Medical mycology journal. 2012;53(4).
29. Flavia Chiva Carvalho MLB, Raul Cesar Evangelista, Maria Palmira Daflon Gremiao. mucoadhesive drug delivery systems. Braziliam journal of pharmaceutical sciences. 2010;46(1).
30. Srikantha T, Tsai LK, Daniels K, Soll DR. EFG1 Null Mutants of Candida albicansSwitch but Cannot Express the Complete Phenotype of White-Phase Budding Cells. Journal of bacteriology. 2000;182(6):1580-91.
Infection Epidemiology and Microbiology
Volume 7, Issue 3
July 2021
Pages 229-236