title: Evaluation of physicochemical properties, skin permeation and accumulation profiles of salicylic acid amide prodrugs as sunscreen agent.
abstract: Various amide prodrugs of salicylic acid were synthesised, and their physicochemical properties including lipophilicity, chemical stability and enzymatic hydrolysis were investigated. In vivo skin permeation and accumulation profiles were also evaluated using a combination of common permeation enhancing techniques such as the use of a supersaturated solution of permeants in an enhancer vehicle, a lipophilic receptor solution, removal of the stratum corneum and delipidisation of skin. Their capacity factor values were proportional to the degree of carbon-carbon saturation in the side chain. All these amides were highly stable in acetonitrile and glycerine. Amide prodrugs were converted to salicylic acid both in hairless mouse liver and skin homogenates. N-dodecyl salicylamide (C12SM) showed the lowest permeation of salicylic acid in skin compared to the other prodrugs, probably due to its low aqueous solubility. It had a high affinity for the stratum corneum and its accumulation was restricted to only the uppermost layer of skin. Thus, this amide prodrug could be a safer topical sunscreen agent with minimum potential for systemic absorption.
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1 Dae-Dong, Gyungsan, Gyungbuk 712-749, South Korea.
authors.forename: Yi-Dong
authors.initials: YD
authors.lastname: Yan
authors.forename: Jun Ho
authors.initials: JH
authors.lastname: Sung
authors.forename: Dong Won
authors.initials: DW
authors.lastname: Lee
authors.forename: Jung Sun
authors.initials: JS
authors.lastname: Kim
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Jeon
authors.forename: Dae-Duk
authors.initials: DD
authors.lastname: Kim
authors.forename: Dong Wuk
authors.initials: DW
authors.lastname: Kim
authors.forename: Jong Oh
authors.initials: JO
authors.lastname: Kim
authors.forename: Ming Guan
authors.initials: MG
authors.lastname: Piao
authors.forename: Dong Xun
authors.initials: DX
authors.lastname: Li
authors.forename: Chul Soon
authors.initials: CS
authors.lastname: Yong
authors.forename: Han Gon
authors.initials: HG
authors.lastname: Choi
mesh_terms: D000279:Administration, Cutaneous; D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D004355:Drug Stability; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D051379:Mice; D008812:Mice, Hairless; D010539:Permeability; D011355:Prodrugs; D012459:Salicylates / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D012995:Solubility; D013473:Sunscreening Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D000577:Amides; D011355:Prodrugs; D012459:Salicylates; D013473:Sunscreening Agents