ABSTRACT
In this study, a liposomal lyophilized powder formulation of panomycocin was developed for therapeutic purposes against vulvovaginal candidiasis which affects 80% of women worldwide. Panomycocin is a potent antimycotic protein secreted by the yeast Wickerhamomyces anomalus NCYC 434. This study involved the preparation of panomycocin-loaded stratum corneum lipid liposomes (SCLLs), characterization of the SCLLs, and determination of antimycotic efficacy of the formulation against Candida albicans and Candida glabrata clinical vaginal isolates in a human vaginal epithelium tissue model. The encapsulation and loading efficiencies of SCLLs were 73% and 76.8%, respectively. In transmission electron microscopy images, the SCLLs appeared in the submicron size range. Dynamic light scattering analyses showed that the SCLLs had uniform size distribution. Zeta potential measurements revealed stable and positively charged SCLLs. In Fourier transform infrared spectroscopy analyses, no irreversible interactions between the encapsulated panomycocin and the SCLLs were detected. The SCLLs retained >98% of encapsulated panomycocin in aqueous solution up to 12 hours. The formulation was fungicidal at the same minimum fungicidal concentration values for non-formulated pure panomycocin when tested on an in vitro model of vaginal candidiasis. This is the first study in which SCLLs and a protein as an active ingredient have been utilized together in a formulation. The results obtained in this study led us to conduct further preclinical trials of this formulation for the development of an effective topical anti-candidal drug with improved safety.
Subject(s)
Antifungal Agents/pharmacology , Candidiasis, Vulvovaginal/drug therapy , Glycoside Hydrolases/chemistry , Glycoside Hydrolases/pharmacology , Liposomes/chemistry , Mycotoxins/chemistry , Mycotoxins/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/therapeutic use , Candida albicans/drug effects , Candida albicans/isolation & purification , Candida albicans/pathogenicity , Candida glabrata/drug effects , Candida glabrata/isolation & purification , Candida glabrata/pathogenicity , Candidiasis, Vulvovaginal/microbiology , Drug Delivery Systems , Epithelium/chemistry , Female , Freeze Drying , Humans , Lipids/chemistry , Powders , Spectroscopy, Fourier Transform InfraredABSTRACT
Panomycocin, a novel exo-beta 1,3 glucanase, was tested as an antifungal agent against green and blue mold diseases, the most important causes of post harvest decay in citrus fruits. All tested isolates of Penicillium digitatum and Penicillium italicum were susceptible to panomycocin in vitro. Effective panomycocin concentrations for 50% growth inhibition (MIC-2) for P. digitatum and P. italicum were 2 and 1 microg ml(-1), respectively. Complete (MIC-0) growth inhibition of all isolates observed at a panomycocin concentration of 16 microg ml(-1). Treatment of spores with panomycocin at values lower than the MIC-0 led to slower germ tube elongation and mycelium growth. In tests on fruit, panomycocin at concentrations equal to in vitro MIC-0 value protected lemon fruit from decay.
