title: Increased therapeutic efficacy of a newly synthesized tyrosinase inhibitor by solid lipid nanoparticles in the topical treatment of hyperpigmentation.
abstract: Hyperpigmentation caused by melanin overproduction is a major skin disorder in humans. Inhibition of tyrosinase, a key regulator of melanin production, has been used as an effective strategy to treat hyperpigmentation. In this study, we investigated the use of solid lipid nanoparticles (SLNs) as a highly effective and nontoxic means to deliver a newly synthesized potent tyrosinase inhibitor, MHY498, and to target melanocytes through the skin. MHY498-loaded SLNs (MHY-SLNs) were prepared by an oil-in-water emulsion solvent-evaporation method, and their morphological and physicochemical properties were characterized. MHY-SLNs showed a prolonged drug-release profile and higher skin permeation than that of MHY solution. In an in vivo evaluation of antimelanogenic activity, MHY-SLNs showed a prominent inhibitory effect against ultraviolet B-induced melanogenesis, resulting in no change in the skin color of C57BL/6 mouse, compared with that observed in an MHY solution-treated group and an untreated control group. The antimelanogenic effect of MHY-SLNs was further confirmed through Fontana-Masson staining. Importantly, MHY-SLNs did not induce any toxic effects in the L929 cell line. Overall, these data indicate that MHY-SLNs show promise in the topical treatment of hyperpigmentation.
authors.affiliation: College of Pharmacy, Pusan National University, Busan, South Korea.
authors.forename: Md
authors.initials: M
authors.lastname: Al-Amin
authors.affiliation: College of Pharmacy, Pusan National University, Busan, South Korea.
authors.forename: Jiafu
authors.initials: J
authors.lastname: Cao
authors.affiliation: College of Pharmacy, Pusan National University, Busan, South Korea.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Naeem
authors.affiliation: College of Pharmacy, Pusan National University, Busan, South Korea.
authors.forename: Hasanul
authors.initials: H
authors.lastname: Banna
authors.affiliation: College of Pharmacy, Pusan National University, Busan, South Korea.
authors.forename: Min-Soo
authors.initials: MS
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Pusan National University, Busan, South Korea.
authors.forename: Yunjin
authors.initials: Y
authors.lastname: Jung
authors.affiliation: College of Pharmacy, Pusan National University, Busan, South Korea.
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
authors.affiliation: College of Pharmacy, Pusan National University, Busan, South Korea.
authors.forename: Hyung Ryong
authors.initials: HR
authors.lastname: Moon
authors.affiliation: College of Pharmacy, Pusan National University, Busan, South Korea.
authors.forename: Jin-Wook
authors.initials: JW
authors.lastname: Yoo
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D007700:Kinetics; D008055:Lipids / Q000737:chemistry*; D008543:Melanins / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D053758:Nanoparticles; D036103:Nanotechnology; D010539:Permeability; D012867:Skin / Q000187:drug effects* / Q000201:enzymology / Q000528:radiation effects; D012869:Skin Absorption; D012880:Skin Pigmentation / Q000187:drug effects*; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: C585780:(Z)-5-(2,4-dihydroxybenzylidene)thiazolidine-2,4-dione; D004337:Drug Carriers; D004791:Enzyme Inhibitors; D008055:Lipids; D008543:Melanins; D045162:Thiazolidinediones; D014446:Tyrosine 3-Monooxygenase
keywords: MHY498; hyperpigmentation; melanogenesis; skin delivery; solid lipid nanoparticles