Advanced search
Start date
Betweenand

Design, chemical synthesis and application of histatin-5 peptide fragments associated with liposomal systems to fight the fungus Candida albicans: a new alternative for the treatment of oral candidiasis

Grant number: 22/07949-5
Support Opportunities:Regular Research Grants
Duration: February 01, 2023 - January 31, 2025
Field of knowledge:Physical Sciences and Mathematics - Chemistry
Principal Investigator:Saulo Santesso Garrido
Grantee:Saulo Santesso Garrido
Host Institution: Instituto de Química (IQ). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Currently approximately 75 to 88% of fungal infections are caused by Candida species. Candida albicans is the main microorganism causing these infections, which can start in the form of oral candidiasis and, without proper treatment, progress to a more serious systemic infection. This species of fungus already shows resistance against the main drugs used for treatment. In this case, the most commonly used antifungals, such as polyenes (nystatin and amphotericin B) or azoles (itraconazole, miconazole, fluconazole) do not have an effective action, which makes necessary search for new treatment options and new molecules that are effective in the fight with these microorganisms. In this context, the Histatin family peptides are seen as promising molecules, mainly due to their strong antimicrobial action against C. albicans. Histatin-5, a peptide naturally found in human saliva, inside the parotid salivary glands, is the most effective antifungal in this family. However, it is not yet used in clinical treatment. One of the reasons is its rapid degradation when in contact with human saliva, due to the action of proteases, in addition to the inactivation of its antimicrobial effect due to interaction with enzymes present in saliva. To enable the clinical application of this peptide, it is important to develop a way to improve its action and to allowing the application of this peptide in oral lesions. In this sense, this project proposes the rational design and the use of the solid phase peptide synthesis technique (SPPS) as a strategy to produce peptides analogous to Histatin-5 that present better antifungal action and slower degradation in contact with saliva. Furthermore, the development of liposomes incorporated with these peptides is proposed to protect them from degradation and inactivation of their antimicrobial activities, caused by elements present in the oral environment. The liposomes will be produced by sonication techniques and characterized by size distribution, polydispersity index and zeta potential using light scattering technique, as well as analyzed by transmission electron microscopy. Efficiency studies of the encapsulation of the peptides in liposomes will be carried out and the stability of each system will be evaluated. Cell death kinetic assays for C. albicans and analysis of the degradation of peptides encapsulated in liposomes in human saliva will be performed. At the end of the project, it is intended to obtain a liposomal system that provides an increase in the permanence time of the peptides in the site of action and a certain protection against proteolytic degradation. This would promote an improvement in the antifungal action of antimicrobial peptides (AMPs) derived from Histatin-5, resulting in an alternative treatment for oral candidiasis. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
Articles published in other media outlets (0 total):
More itemsLess items
VEICULO: TITULO (DATA)
VEICULO: TITULO (DATA)

Please report errors in scientific publications list using this form.