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Published on: September 16, 2022
The Influence of Cellulose-Type Formulants on Anti-Candida Activity of the Tyrocidines
Yasamin Masoudi1, Wilma van Rensburg1, Bernice Barnard-Jenkins1
1BIOPEPTM Peptide Group, Department Biochemistry, Stellenbosch University, Private Bag X1, Matieland, Stellenbosch 7602, South Africa.
Abstract:
Candida species are highly adaptable to environmental changes with their phenotypic flexibility allowing for the evasion of most host defence mechanisms. Moreover, increasing resistance of human pathogenic Candida strains has been reported against all four classes of available antifungal drugs, which highlights the need for combinational therapies. Tyrocidines are cyclic antimicrobial peptides that have shown synergistic activity with antifungal drugs such as caspofungin and amphotericin B. However, these cyclodecapeptides have haemolytic activity and cytotoxicity, but they have been used for decades in the clinic for topical applications. The tyrocidines tend to form higher-order structures in aqueous solutions and excessive aggregation can result in variable or diminished activity. Previous studies have shown that the tyrocidines prefer ordered association to celluloses. Therefore, a formulation with soluble cellulose was used to control the oligomer stability and size, thereby increasing the activity against Candida spp. Of the formulants tested, it was found that commercial hydroxy-propyl-methyl cellulose, E10M, yielded the best results with increased stability, increased anti-Candida activity, and improved selectivity. This formulation holds promise in topical applications against Candida spp. infections.
Insights
This study enhances tyrocidine activity against Candida by formulating it with hydroxy-propyl-methyl cellulose. This approach improves stability and selectivity for topical antifungal applications.
Area of Science:
- Microbiology
- Biochemistry
- Drug Discovery
Background:
- Candida species exhibit phenotypic flexibility, aiding immune evasion.
- Increasing antifungal drug resistance necessitates novel therapeutic strategies.
- Tyrocidines, cyclic antimicrobial peptides, show synergistic potential but face challenges with cytotoxicity and aggregation.
Purpose of the Study:
- To develop a stable and effective formulation of tyrocidines for enhanced anti-Candida activity.
- To investigate the role of cellulose-based formulants in controlling tyrocidine aggregation and activity.
- To improve the selectivity of tyrocidine formulations for topical applications.
Main Methods:
- Formulation of tyrocidines with various soluble celluloses, including hydroxy-propyl-methyl cellulose (E10M).
- Assessment of tyrocidine stability, aggregation, and anti-Candida activity in different formulations.
- Evaluation of formulation selectivity and potential for topical applications.
Main Results:
- Hydroxy-propyl-methyl cellulose (E10M) demonstrated superior performance among tested formulants.
- The E10M formulation significantly increased tyrocidine stability and anti-Candida efficacy.
- Improved selectivity was observed with the E10M formulation, reducing potential side effects.
Conclusions:
- Formulating tyrocidines with hydroxy-propyl-methyl cellulose (E10M) offers a promising strategy to enhance their stability and anti-Candida activity.
- This formulation shows potential for effective and selective topical treatment of Candida infections.
- Controlling tyrocidine oligomerization through formulation is key to optimizing its therapeutic utility.
