A Novel Antifungal System With Potential for Prolonged Delivery of Histatin 5 to Limit Growth of Candida albicans
Currently 75–88% of fungal infections are caused by Candida species, and Candida albicans is the main microorganism that causes these infections, especially oral candidiasis. An option for treatment involves the use of the antifungal peptide Histatin 5 (Hst 5), which is naturally found in human sali...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-07-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2019.01667/full |
| _version_ | 1819072678637600768 |
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| author | Carolina R. Zambom Fauller H. da Fonseca Edson Crusca Patrícia B. da Silva Fernando R. Pavan Marlus Chorilli Saulo S. Garrido |
| author_facet | Carolina R. Zambom Fauller H. da Fonseca Edson Crusca Patrícia B. da Silva Fernando R. Pavan Marlus Chorilli Saulo S. Garrido |
| author_sort | Carolina R. Zambom |
| collection | DOAJ |
| description | Currently 75–88% of fungal infections are caused by Candida species, and Candida albicans is the main microorganism that causes these infections, especially oral candidiasis. An option for treatment involves the use of the antifungal peptide Histatin 5 (Hst 5), which is naturally found in human saliva but undergoes rapid degradation when present in the oral cavity, its site of action. For this reason, it is important to develop a way of applying this peptide to the oral lesions, which promotes the gradual release of the peptide. In the present study, we have evaluated the development of liposomes of different lipid compositions, loaded with the peptide as a way to promote its release slowly and gradually, preserving its antifungal potential. For this, the peptide 0WHistatin 5, an analog of the peptide Hst 5, was synthesized, which contains the amino acid tryptophan in its sequence. The solid phase synthesis method was used, followed by cleavage and purification. The liposomes were produced by thin film hydration technique in three different lipid compositions, F1, F2, and F3 and were submitted to an extrusion and sonication process to standardize the size and study the best technique for their production. The liposomes were characterized by dynamic light scattering, and tests were performed to determine the encapsulation efficiency, release kinetics, stability, and evaluation of antifungal activity. The extruded liposomes presented average size in the range of 100 nm, while sonicated liposomes presented a smaller size in the range of 80 nm. The encapsulation efficiency was higher for the sonicated liposomes, being 34.5% for F1. The sonicated F3 presented better stability when stored for 60 days at 4°C. The liposomes showed the ability to release the peptide for the total time of 96 h, with the first peak after 5 h, and a further increase of the released after 30 h. Time-kill assay showed that the liposomes were able to control yeast growth for 72 h. The data suggest that the liposomes loaded with 0WHistatin 5 maintained the action of the peptide and were able to limit the growth of C. albicans, being a suitable system for use in the treatment of oral candidiasis. |
| first_indexed | 2024-12-21T17:41:33Z |
| format | Article |
| id | doaj.art-afcc9de5bf0f4be6b869b78ef614b8d6 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-21T17:41:33Z |
| publishDate | 2019-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-afcc9de5bf0f4be6b869b78ef614b8d62022-12-21T18:55:36ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2019-07-011010.3389/fmicb.2019.01667440167A Novel Antifungal System With Potential for Prolonged Delivery of Histatin 5 to Limit Growth of Candida albicansCarolina R. Zambom0Fauller H. da Fonseca1Edson Crusca2Patrícia B. da Silva3Fernando R. Pavan4Marlus Chorilli5Saulo S. Garrido6Department of Biochemistry and Chemical Technology, Institute of Chemistry, UNESP – São Paulo State University, Araraquara, BrazilDepartment of Biochemistry and Chemical Technology, Institute of Chemistry, UNESP – São Paulo State University, Araraquara, BrazilDepartment of Biochemistry and Chemical Technology, Institute of Chemistry, UNESP – São Paulo State University, Araraquara, BrazilDepartment of Biological Sciences, School of Pharmaceutical Sciences of Araraquara, UNESP – São Paulo State University, Araraquara, BrazilDepartment of Drugs and Medicines, School of Pharmaceutical Sciences of Araraquara, UNESP – São Paulo State University, Araraquara, BrazilDepartment of Biological Sciences, School of Pharmaceutical Sciences of Araraquara, UNESP – São Paulo State University, Araraquara, BrazilDepartment of Biochemistry and Chemical Technology, Institute of Chemistry, UNESP – São Paulo State University, Araraquara, BrazilCurrently 75–88% of fungal infections are caused by Candida species, and Candida albicans is the main microorganism that causes these infections, especially oral candidiasis. An option for treatment involves the use of the antifungal peptide Histatin 5 (Hst 5), which is naturally found in human saliva but undergoes rapid degradation when present in the oral cavity, its site of action. For this reason, it is important to develop a way of applying this peptide to the oral lesions, which promotes the gradual release of the peptide. In the present study, we have evaluated the development of liposomes of different lipid compositions, loaded with the peptide as a way to promote its release slowly and gradually, preserving its antifungal potential. For this, the peptide 0WHistatin 5, an analog of the peptide Hst 5, was synthesized, which contains the amino acid tryptophan in its sequence. The solid phase synthesis method was used, followed by cleavage and purification. The liposomes were produced by thin film hydration technique in three different lipid compositions, F1, F2, and F3 and were submitted to an extrusion and sonication process to standardize the size and study the best technique for their production. The liposomes were characterized by dynamic light scattering, and tests were performed to determine the encapsulation efficiency, release kinetics, stability, and evaluation of antifungal activity. The extruded liposomes presented average size in the range of 100 nm, while sonicated liposomes presented a smaller size in the range of 80 nm. The encapsulation efficiency was higher for the sonicated liposomes, being 34.5% for F1. The sonicated F3 presented better stability when stored for 60 days at 4°C. The liposomes showed the ability to release the peptide for the total time of 96 h, with the first peak after 5 h, and a further increase of the released after 30 h. Time-kill assay showed that the liposomes were able to control yeast growth for 72 h. The data suggest that the liposomes loaded with 0WHistatin 5 maintained the action of the peptide and were able to limit the growth of C. albicans, being a suitable system for use in the treatment of oral candidiasis.https://www.frontiersin.org/article/10.3389/fmicb.2019.01667/fullantifungal systemoral candidiasisCandida albicansHistatin 5liposomes |
| spellingShingle | Carolina R. Zambom Fauller H. da Fonseca Edson Crusca Patrícia B. da Silva Fernando R. Pavan Marlus Chorilli Saulo S. Garrido A Novel Antifungal System With Potential for Prolonged Delivery of Histatin 5 to Limit Growth of Candida albicans Frontiers in Microbiology antifungal system oral candidiasis Candida albicans Histatin 5 liposomes |
| title | A Novel Antifungal System With Potential for Prolonged Delivery of Histatin 5 to Limit Growth of Candida albicans |
| title_full | A Novel Antifungal System With Potential for Prolonged Delivery of Histatin 5 to Limit Growth of Candida albicans |
| title_fullStr | A Novel Antifungal System With Potential for Prolonged Delivery of Histatin 5 to Limit Growth of Candida albicans |
| title_full_unstemmed | A Novel Antifungal System With Potential for Prolonged Delivery of Histatin 5 to Limit Growth of Candida albicans |
| title_short | A Novel Antifungal System With Potential for Prolonged Delivery of Histatin 5 to Limit Growth of Candida albicans |
| title_sort | novel antifungal system with potential for prolonged delivery of histatin 5 to limit growth of candida albicans |
| topic | antifungal system oral candidiasis Candida albicans Histatin 5 liposomes |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2019.01667/full |
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