Mustafa KOTMAKÇI, Yücel BAŞPINAR, İsmail ÖZTÜRK

Antimicrobial Activity of Phytosphingosine Nanoemulsions against Bacteria and Yeasts

Phytosphingosine (PS) is a natural antimicrobial ingredient present in the mammalian stratum corneum ofthe skin. The skin surface is the first line defense system against microbial colonization and infections. Theaim of this study was to investigate in vitro antimicrobial effects of PS and PS-hydrochloride (PSHCl)nanoemulsion (NE) formulations and solutions against bacteria and fungi. Minimum inhibitoryconcentrations (MICs) of the PS-NE and PSHCl-NE formulations and PS/PSHCl solutions were determinedby microdilution method against Gram-positive/Gram-negative bacteria and yeasts. Inhibitory effects werealso examined by disc diffusion method and inhibition zone diameters were determined. PS/PSHCl solutionsand PS-NE/PSHCl-NE formulations were prepared in different conditions. Physicochemical properties of theNEs were characterized and antimicrobial activities were evaluated. In this study we reported that the PS andPSHCl and NEs had variable antimicrobial activities for a variety of Gram-positive bacteria (MIC range 1μg/ml to 1024 μg/ml), Gram-negative bacteria (MIC range 8 μg/ml to 1024 μg/ml) and Candida strains (MICrange 8 μg/ml to 512 μg/ml). Sphingolipids are part of the natural defense system of the body. Wedemonstrated that PS and PSHCl solutions and NEs have broad antimicrobial activity against bacteria andyeasts. In addition, the newly developed formulations may have potential for prophylactic and therapeuticintervention in infections.

PDF

___

Wolf, F, Juestel, C, Schreiber, J, Klier, M, Sphingolipids as antimicrobial agents, German Patent 1997, 19602108.
Lersch, P, Schick, U, Choosing the right ingredients for cosmeceuticals, Speciality Chemicals Magazine, 2003, 23, 30-31.
Rawlings, A.V, 2003. Trends in stratum corneum research and the management of dry skin conditions, International Journal of Cosmetic Science, 53, 63–95.
Drake, D.R, Brogden, K.A, Dawson, D.V, Wertz, P.W, Thematic review series: skin lipids. Antimicrobial lipids at the skin surface. Journal of Lipid Research, 2008, 49, 4 –11.
Mason, T.G, Wilking, J.N, Meleson, K, Chang, C.B, Graves, S.M, Nanoemulsions: Formation, structure and physical properties. Journal of Physics: Condensed Matter, 2006, 18, 635–666.
Fischer, C.L, Drake D.R, Dawson D.V, Blanchette, D.R, Brogden, K.A, Wertz P.W, Antibacterial Activity of Sphingoid Bases and Fatty Acids against GramPositive and Gram-Negative Bacteria, Antimicrobial Agents and Chemotherapy, 2012, 56(3), 1157-1161.
Drake, D.R, Brogden, K.A, Dawson, D.V, Wertz, P.W, Thematic review series: skin lipids. Antimicrobial lipids at the skin surface. Journal of Lipid Research, 2008, 49, 4–11.
Pavicic, T, Wollenweber, U, Farwick, M, Korting, H.C, Anti- microbial and -inflammatory activity and efficacy of phytosphingosine: an in vitro and in vivo study addressing acne vulgaris. International Journal of Cosmetic Science, 2007, 29, 181–190.
Hoeller, S, Sperger, A, Valenta, C, Lecithin based nanoemulsions: a comparative study of the influence of non-ionic surfactants and the cationic phytosphingosine on physicochemical behaviour and skin permeation. International Journal of Pharmaceutics, 2009, 370, 181–186.
Gupta, A.K, Fisher, G.J, Elder, J.T, Nickoloff, B.J, Voorhees, J.J, Sphingosine inhibits phorbol esterinduced inflammation, ornithine decarboxylase activity, and activation of protein kinase C in mouse skin. Journal of Investigative Dermatology, 1988, 91, 486–491.
Bibel, D.J, Aly, R, Shinefield, H.R, Antimicrobial activity of spingosines. Journal of Investigative Dermatology, 1992, 98, 269– 273.
Gupta, A.K, Fisher, G.J, Elder, J.T, Nickoloff, B.J, Voorhees, J.J, Sphingosine inhibits phorbol esterinduced inflammation, ornithine decarboxylase activity, and activation of protein kinase C in mouse skin. Journal of Investigative Dermatology, 1988, 91, 486–491.
Bergsson, G, Arnfinnsson, J, Steingrimsson, O, Thormar, H, In vitro killing of Candida albicans by fatty acids and monoglycerides, Antimicrobial Agents and Chemotherapy, 2001, 45, 3209 –3212.
Baspinar, Y, and Borchert, H.H, Penetration and release studies of positively and negatively charged nanoemulsions—Is there a benefit of the positive charge? International Journal of Pharmaceutics, 2012, 430, 247-252.
Bibel, D.J, Aly, R, Shinefield, H.R, Antimicrobial activity of spingosines. Journal of Investigative Dermatology, 1992, 98, 269– 273.
Kotmakçı, M, Öztürk, İ, Kantarcı, G, Ermertcan, Ş. Characterization and antimicrobial activity of novel hazelnut oil microemulsion loaded with Mitomycin C. Latin American Journal of Pharmacy, 2015, 34: 529– 36.
Veerman, E.C, Valentijn-Benz, M, van't Hof, W, Nazmi, K, van Marle, J, Amerongen, A.V, Phytosphingosine kills Candida albicans by disrupting its cell membrane, Biological Chemistry, 2010, 391(1), 65-71.
Garg, S.K, Volpe, E, Palmiero, G, Mattei, M, Galati, D, Martino, A, Piccioni, M.S, Valente, E, Bonanno, E, De Vito, P, Baldini, P.M, Spagnoli, L.G, Cilizzi, V, Fraziano, M, Sphingosine 1- phosphate induces antimicrobial activity both in vitro and in vivo. Journal of Infectious Diseases, 2004, 189, 2129–2138.
Baspinar, Y, and Borchert, H.H, Penetration and release studies of positively and negatively charged nanoemulsions—Is there a benefit of the positive charge? International Journal of Pharmaceutics, 2012, 430, 247-252.
Kotmakçı, M, Öztürk, İ, Kantarcı, G, Ermertcan, Ş. Characterization and antimicrobial activity of novel hazelnut oil microemulsion loaded with Mitomycin C. Latin American Journal of Pharmacy, 2015, 34: 529– 36.
Baspinar, Y, Keck, C, Borchert, H.H, Development of a positively charged prednicarbate nanoemulsion, International Journal of Pharmaceutics, 2010, 383, 201–208.
Fischer, C.L, Walters, K.S, Drake, D.R, Blanchette, D.R, Dawson, D.V, Brogden, K.A, Wertz, P.W, Sphingoid bases are taken up by Escherischia coli and Staphylococcus aureus and induce ultrastructural damage, Skin Pharmacology and Physiology, 2013, 26, 36–44.
Fischer, C.L, Blanchette, D.R, Brogden, K.A, Dawson, D.V, Drake, D.R, Hill, J.R, Wertz, P.W, The roles of cutaneous lipids in host defense, Biochimica et Biophysica Acta, 2014, 1841(3), 319322.
Fischer, C.L, Blanchette, D.R, Brogden, K.A, Dawson, D.V, Drake, D.R, Hill, J.R, Wertz, P.W, The roles of cutaneous lipids in host defense, Biochimica et Biophysica Acta, 2014, 1841(3), 319322.
Hasanovic, A, Hoeller, S, Valenta, C, Analysis of skin penetration of phytosphingosine by fluorescence detection and influence of the thermotropic behaviour of DPPC liposomes, International Journal of Pharmaceutics, 2010, 4, 383(1-2), 14-17.