Delivered by Ingenta to: University of South Carolina IP: 185.46.86.126 On: Mon, 05 Dec 2016 11:32:59 Copyright: American Scientific Publishers Copyright © 2013 American Scientific Publishers All rights reserved Printed in the United States of America Article Journal of Biomedical Nanotechnology Vol. 9, 626–638, 2013 www.aspbs.com/jbn Melanogenesis of Methyl Myristate Loaded Niosomes in B16F10 Melanoma Cells Aranya Manosroi 1 2 ∗ , Puxvadee Chaikul 1 , Masahiko Abe 3 , Worapaka Manosroi 4 , and Jiradej Manosroi 1 2 1 Faculty of Pharmacy, Department of Pharmaceutical Science, Chiang Mai University, Chiang Mai 50200, Thailand 2 Natural Products Research and Development Center (NPRDC) Science and Technology Research Institute, Chiang Mai University, Chiang Mai 50200, Thailand 3 Faculty of Science and Technology, Department of Pure and Applied Chemistry, Tokyo University of Science, 2641 Chiba, Japan 4 Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand The objective of this study was to compare the charge effect of methyl myristate loaded in neutral (Brij 72/cholesterol at 7:3), cationic (Brij 72/cholesterol/dimethyl dioctadecyl ammonium bromide at 7:3:0.65) and anionic niosomes (Brij 72/cholesterol/dicetyl phosphate at 7:3:0.65) for physicochemical characteristics, cytotoxicity in fibroblasts and B16F10 melanoma cells as well as melanogenesis induction activity. The maximum loading and percentage entrapment of methyl myristate were 4.5, 9068 ±795 in neutral; 11.0, 9254 ±632 in cationic and 0.1% w/w, 7443 ±186% in anionic niosomes, respectively. All methyl myristate loaded niosomes were in unilamellar structure under transmission electron microscope and in nanosize at initial and after 3-month storage. The percentages of methyl myristate remaining in all niosomes kept at 4 ± 2, 30 ± 2 and 45 ± 2  C for 3 months were about 82, 74 and 72%, respectively, while the dry free methyl myristate indicated 9782 ± 174, 9656 ± 291 and 9139 ± 432%, respectively. Blank neutral, blank cationic and methyl myristate loaded neutral and cationic niosomes exhibited moderate cytotoxicity in fibroblasts and B16F10 melanoma cells at 5664 ± 319, 5972 ± 151; 7381 ± 286, 8251 ± 020; 4734 ± 213, 5267 ± 278 and 7320 ± 349, 8434 ± 275% cell viability, respectively. Blank anionic and methyl myristate loaded anionic niosomes indicated no cytotoxicity in both cells. Cytotoxic ratio of cell viability in normal and cancer cells of all niosomes indicated no toxic effect to normal cells. Methyl myristate loaded cationic niosomes demonstrated the highest melanin induction with tyrosinase activity of 1.42 and 1.70 folds of the control and 1.14 and 1.59 folds higher than theophylline, respectively. This study has suggested the potential of methyl myristate loaded cationic niosomes for canities treatment. KEYWORDS: Methyl Myristate, Cationic Niosomes, Cytotoxicity, Melanogenesis Induction, Canities. INTRODUCTION Non-ionic surfactant vesicles or niosomes are the closed bilayer structures similar to liposomes which are made of amphiphiles in aqueous media. Liposomes are composed of phospholipids, while niosomes are consisted of non-ionic surfactants. Cholesterol is generally incorporated into these structures in order to alter the fluidity of membranes in the bilayers. When presenting in a sufficient concentration, cholesterol can abolish the gel to liquid phase transition endotherm of the bilayers. These closed bilayer systems ∗ Author to whom correspondence should be addressed. Emails: a.manosroi@gmail.com, pmpti005@chiangmai.ac.th Received: 4 April 2012 Accepted: 16 September 2012 consisted of hydrophobic parts and hydrophilic groups can entrap both hydrophobic and hydrophilic substances and serve as the drug, cosmetic and plant extract delivery sys- tems. Also, they exhibit the modification of the pharma- cokinetics and pharmacodynamics, low toxicity as well as the environmental protection of the entrapped compounds. In comparison to liposomes, niosomes demonstrate greater chemical stability, lower cost and less vesicular aggregation and fusion than liposomes. 1–4 The charge of niosomal vesi- cles prepared without the inclusion of charged molecules usually shows the negative zeta potential because of the preferential adsorption of the hydroxyl (OH - ) ions at the surface of the vesicles. In fact, the vesicular surface charge is important to prevent aggregation due to the shielding of 626 J. Biomed. Nanotechnol. 2013, Vol. 9, No. 4 1550-7033/2013/9/626/013 doi:10.1166/jbn.2013.1565