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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Incorporation of Nonyl 3,4-Dihydroxybenzoate Into Nanostructured Lipid Systems: Effective Alternative for Maintaining Anti-Dermatophytic and Antibiofilm Activities and Reducing Toxicity at High Concentrations

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Author(s):
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Costa-Orlandi, Caroline Barcelos [1] ; Serafim-Pinto, Aline [1] ; da Silva, Patricia Bento [2] ; Bila, Niura Madalena [1, 3] ; de Carvalho Bonatti, Jean Lucas [1] ; Scotzoni, Liliana [1] ; Singulani, Junya de Lacorte [1] ; dos Santos, Claudia Tavares [1] ; Nazare, Ana Carolina [4] ; Chorilli, Marlus [2] ; Regasini, Luis Octavio [4] ; Fusco-Almeida, Ana Marisa [1] ; Soares Mendes-Giannini, Maria Jose [1]
Total Authors: 13
Affiliation:
[1] Univ Estadual Paulista UNESP, Sch Pharmaceut Sci, Dept Clin Anal, Araraquara, SP - Brazil
[2] Univ Estadual Paulista UNESP, Sch Pharmaceut Sci, Dept Drugs & Med, Araraquara, SP - Brazil
[3] Univ Eduardo Mondlane, Sch Vet, Maputo - Mozambique
[4] Univ Estadual Paulista UNESP, Inst Biosci Humanities & Exact Sci, Dept Chem & Environm Sci, Sao Jose Do Rio Preto - Brazil
Total Affiliations: 4
Document type: Journal article
Source: FRONTIERS IN MICROBIOLOGY; v. 11, JUN 5 2020.
Web of Science Citations: 0
Abstract

Dermatophytosis is the most common mycosis worldwide, affecting approximately 20 to 25% of the population, regardless of gender, race, color, and age. Most antifungal agents used for the treatment of dermatophytosis belong to the azole and allylamine classes. Dermatophytes are reported to be resistant to most commercial drugs, especially microbial biofilms, in addition to their considerable toxicity. It should be emphasized the importance of looking for new molecules with reduced toxicity, as well as new targets and mechanisms of action. This work aims to incorporate nonyl 3,4-dihydroxybenzoate, a potent fungicide compound against planktonic cells and dermatophyte biofilms in nanostructured lipid systems (NLS), in order to reduce toxicity in high concentrations, improve its solubility and maintain its effectiveness. The compound was incorporated into NLS constituted by cholesterol, mixture of polyoxyethylene (23) lauryl ether (Brij(R)98) and soybean phosphatidylcholine (Epikuron(R)200)], 2: 1 ratio and PBS (phosphate-buffered saline). The characterization of the incorporation was performed. Susceptibility tests were conducted according to document M38-A2 byCLSI (2008). The toxicity of the NLS compound was evaluated in HaCaT cell lines by the sulforhodamine B method and in alternative modelsCaenorhabditis elegansand zebrafish. Finally, its efficacy was evaluated against the matureTrichophyton rubrumandTrichophyton mentagrophytesbiofilms. NLS and nonyl 3,4-dihydroxybenzoate loaded into NLS displayed sizes ranging from 137.8 +/- 1.815 to 167.9 +/- 4.070 nm; the polydispersity index (PDI) varying from 0.331 +/- 0.020 to 0.377 +/- 0.004 and zeta potential ranging from -1.46 +/- 0.157 to -4.63 +/- 0.398 mV, respectively. Polarized light microscopy results confirmed the formation of NLS of the microemulsion type. Nonyl incorporated into NLS showed minimum inhibitory concentration (MIC) values, ranging from 2 to 15.6 mg/L. The toxicity tests presented cell viability higher than 80% in all tested concentrations, as well as, a significantly increased of the survival ofCaenorhabditis elegansand zebrafish models. Anti-biofilm tests proved the efficacy of the incorporation. These findings contribute significantly to the search for new antifungals and allow the systemic administration of the compound, since the incorporation can increase the solubility of non-polar compounds, improve bioavailability, effectiveness and reduce toxicity. (AU)

FAPESP's process: 18/02785-9 - Dermatophytes and Dermatophytosis: biofilm formation and development of control strategies.
Grantee:Maria José Soares Mendes Giannini
Support Opportunities: Regular Research Grants
FAPESP's process: 17/18388-6 - Role of biofilm in the pathogenesis of dermatophytosis and development of combat strategies
Grantee:Caroline Barcelos Costa Orlandi
Support Opportunities: Scholarships in Brazil - Post-Doctoral