Date

2013

Author

Elçin, Evrim

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There is an increase in the incidence of superficial fungal infections. Especially, immuno-compromised patients, diabetic patients, obese and people having resistancy against a group of antifungal drugs are at great risk. In these patient groups the infection can become chronic and affect the deeper and living layers of the skin and can be life threatening if not treated effectively. However, drugs which are currently used in the therapy of dermatophyte infections are becoming less effective due to the serious side effects and resistance developed by the pathogens. Thus, there is a continuing need for new classes of antifungal compounds that have potent antifungal activity, improved safety and low tendency to elicit resistance. Among the different approaches, the discoveries of naturally occuring antifungal proteins with little or no toxicity towards mammalian cells are attracting increasing attention. Within the naturally occuring antifungal proteins the yeast killer proteins which are produced and secreted into the environment by yeast strains with a killer phenotype represent promising candidates as potential antifungal agents in the medical field. Among the most effective killer toxins, the K5 type toxin has been purified and characterized for the first time in our laboratory and named as Panomycocin. Panomycocin is an exo-β-1,3 glucanase with a molecular mass of 49 kDa. It kills the sensitive cells by hydrolysing the β-1,3-glucans which are vital polymers for the integrity of the fungal cell wall. In following studies we have formulated Panomycocin with chitosan-TPP nanoparticles, which are used for the encapsulation of therapeutic proteins and accepted as effective non-toxic carrier system and characterized the nanoparticles in terms of surface morphology, particle size, zeta potential, interactions between chitosan, TPP and Panomycocin and in vitro release of Panomycocin from chitosan-TPP nanoparticles. Lastly, we have determined in vitro antifungal activity of Panomycocin-incorporated chitosan-TPP nanoparticles against common human dermatophytes. All tested dermatophyte strains were found to be susceptible to Panomycocin-loaded CS-TPP NPs. MIC-0 range for Tricophyton species was found as 1-2 mg/ml and MIC-0 for Microsporum gypseum was found as 1.5 mg/ml. This study will enable the development of a new, highly selective antifungal drug for the topical treatment of human superficial infections. In addition to providing health benefits, Panomycocin will contribute to the economy as it is produced naturally.

Subject Keywords

Dermatophytes., Skin, Skin, Nanoparticles., Chitosan.

URI

http://etd.lib.metu.edu.tr/upload/12616320/index.pdf
https://hdl.handle.net/11511/22920

Collections

Graduate School of Natural and Applied Sciences, Thesis