title: Biodegradable Kojic Acid-Based Polymers: Controlled Delivery of Bioactives for Melanogenesis Inhibition.
abstract: Kojic acid (KA) is a naturally occurring fungal metabolite that is utilized as a skin-lightener and antibrowning agent owing to its potent tyrosinase inhibition activity. While efficacious, KA's inclination to undergo pH-mediated, thermal-, and photodegradation reduces its efficacy, necessitating stabilizing vehicles. To minimize degradation, poly(carbonate-esters) and polyesters comprised of KA and natural diacids were prepared via solution polymerization methods. In vitro hydrolytic degradation analyses revealed KA release was drastically influenced by polymer backbone composition (e.g., poly(carbonate-ester) vs polyester), linker molecule (aliphatic vs heteroatom-containing), and release conditions (physiological vs skin). Tyrosinase inhibition assays demonstrated that aliphatic KA dienols, the major degradation product under skin conditions, were more potent then KA itself. All dienols were found to be less toxic than KA at all tested concentrations. Additionally, the most lipophilic dienols were statistically more effective than KA at inhibiting melanin biosynthesis in cells. These KA-based polymer systems deliver KA analogues with improved efficacy and cytocompatible profiles, making them ideal candidates for sustained topical treatments in both medical and personal care products.
authors.affiliation: Department of Chemistry and Chemical Biology, ‡Ernest Mario School of Pharmacy, and §Department of Chemical & Biochemical Engineering, Rutgers University , Piscataway, New Jersey 08854, United States.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Faig
authors.affiliation: Department of Chemistry and Chemical Biology, ‡Ernest Mario School of Pharmacy, and §Department of Chemical & Biochemical Engineering, Rutgers University , Piscataway, New Jersey 08854, United States.
authors.forename: Alysha
authors.initials: A
authors.lastname: Moretti
authors.affiliation: Department of Chemistry and Chemical Biology, ‡Ernest Mario School of Pharmacy, and §Department of Chemical & Biochemical Engineering, Rutgers University , Piscataway, New Jersey 08854, United States.
authors.forename: Laurie B
authors.initials: LB
authors.lastname: Joseph
authors.affiliation: Department of Chemistry and Chemical Biology, ‡Ernest Mario School of Pharmacy, and §Department of Chemical & Biochemical Engineering, Rutgers University , Piscataway, New Jersey 08854, United States.
authors.forename: Yingyue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Chemistry and Chemical Biology, ‡Ernest Mario School of Pharmacy, and §Department of Chemical & Biochemical Engineering, Rutgers University , Piscataway, New Jersey 08854, United States.
authors.forename: Mary Joy
authors.initials: MJ
authors.lastname: Nova
authors.affiliation: Department of Chemistry and Chemical Biology, ‡Ernest Mario School of Pharmacy, and §Department of Chemical & Biochemical Engineering, Rutgers University , Piscataway, New Jersey 08854, United States.
authors.forename: Kervin
authors.initials: K
authors.lastname: Smith
authors.affiliation: Department of Chemistry and Chemical Biology, ‡Ernest Mario School of Pharmacy, and §Department of Chemical & Biochemical Engineering, Rutgers University , Piscataway, New Jersey 08854, United States.
authors.forename: Kathryn E
authors.identifier: 0000-0001-7273-7528
authors.initials: KE
authors.lastname: Uhrich
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems; D008543:Melanins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D008546:Melanoma, Experimental / Q000188:drug therapy*; D051379:Mice; D041681:NIH 3T3 Cells; D058105:Polymerization; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry*; D011753:Pyrones / Q000737:chemistry*; D014407:Tumor Cells, Cultured
chemical_list: D001672:Biocompatible Materials; D008543:Melanins; D011108:Polymers; D011753:Pyrones; C011890:kojic acid