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]. Cosmet. Sci.) 59, 139-150 (March/April 2008) Enhanced depigmenting effects of N-glycosylation inhibitors delivered by pH-sensitive liposomes into HM3KO melanoma cells JU YOUNG PARK, HYUNJUNG CHOI, JAE SUNG HWANG, JUNOH KIM, and IH-SEOP CHANG, Skin Research Institute) Amore Pacific Corp. R&D Center, 314-1, Bora-dong, Giheung-gu, Yongin-si, Gyeonggi-do, 446-729, Korea. Accepted for publication June 13, 2007. Presented in part at the 23rd Congress of the International Federation of Societies of Cosmetic Chemists (IFSCC), Orlando, Florida, October 2004, and in Proceedings of the IFSCC as "Enhanced Pigment Lightening Effects of N-Glycosylation Inhibitors by the CHEMS Incorporated Nano-Carrier." Synopsis Delivery activity of pH-sensitive 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE):cholesteryl hemi- succinate (CHEMS) liposomes was assessed as an in vitro intracellular carrier system to increase the bio- availability of depigmentation actives. N-glycosylation inhibitors have a glycosylation-inhibiting effect, which is useful for the skin depigmentation that operates by interfering with the maturation of tyrosinase. However, an N-glycosylation inhibitor does not easily pass through skin or even cellular membranes due to its water-soluble property. Therefore, it should be transported to target cells by an efficient delivery carrier to reduce the glycosylated tyrosinase. Glycosylation-inhibiting and depigmentation effects of N- butyldeoxynojirimycine (NB-DNJ) and 1-deoxynojirimycine (DNJ)-loaded liposomes were evaluated using Western blotting and measurement of synthesized melanin. Interestingly, it was found that the pH-sensitive liposomes increased the glycosylation-inhibiting and thus, pigment-lightening effects of N-glycosylation inhibitors in vitro. In addition, cargo materials loaded in pH-sensitive liposomes were found to be much more efficiently delivered into the cytoplasm, as observed in fluorescent-activated cell sorting (FACS) and confocal laser-scanning microscopic (CLSM) analysis. These results indicate that pH-sensitive DOPE: CHEMS liposomes have a strong potential as a carrier system to promote delivery efficiency and to enhance the biological effects of water-soluble actives for applications in cosmetics, personal care products, and pharmaceutics. INTRODUCTION Classic liposomes reaching into a cytoplasmic target site are generally first recognized, taken up by endocytosis, and eventually delivered to lysosomes. Most of these liposomes Address all correspondence to Ju Young Park. 139