title: Lysine-based surfactants as chemical permeation enhancers for dermal delivery of local anesthetics.
abstract: The aim of this study is to investigate the efficacy of new, biocompatible, lysine-based surfactants as chemical permeation enhancers for two different local anesthetics, tetracaine and ropivacaine hydrochloride, topically administered. Results show that this class of surfactants strongly influences permeation, especially in the case of the hydrophilic and ionized drug, ropivacaine hydrochloride, that is not easily administered through the stratum corneum. It is also seen that the selected permeation enhancers do not have significant deleterious effects on the skin structure. A cytotoxicity profile for each compound was established from cytotoxicity studies. Molecular dynamics simulation results provided a rationale for the experimental observations, introducing a mechanistic view of the action of the surfactants molecules upon lipid membranes.
authors.affiliation: Pharmaceutical Technology Department, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal.
authors.forename: Raquel S
authors.initials: RS
authors.lastname: Teixeira
authors.affiliation: Chemistry Department, Faculty of Science and Technology, University of Coimbra, 3004-535 Coimbra, Portugal.
authors.forename: Tânia F G G
authors.initials: TF
authors.lastname: Cova
authors.affiliation: Chemistry Department, Faculty of Science and Technology, University of Coimbra, 3004-535 Coimbra, Portugal.
authors.forename: Sérgio M C
authors.initials: SM
authors.lastname: Silva
authors.affiliation: Life Sciences Department, Fernando Pessoa University, 4249-004 Porto, Portugal.
authors.forename: Rita
authors.initials: R
authors.lastname: Oliveira
authors.affiliation: CIQ-UP, Department of Chemistry and Biochemistry, Faculty of Science, University of Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Araújo
authors.affiliation: CIQ-UP, Department of Chemistry and Biochemistry, Faculty of Science, University of Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal.
authors.forename: Eduardo F
authors.initials: EF
authors.lastname: Marques
authors.affiliation: Life Sciences Department, Fernando Pessoa University, 4249-004 Porto, Portugal.
authors.forename: Alberto A C C
authors.initials: AA
authors.lastname: Pais
authors.affiliation: Pharmaceutical Technology Department, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal. Electronic address: fveiga@ci.uc.pt.
authors.forename: Francisco J B
authors.initials: FJ
authors.lastname: Veiga
mesh_terms: D000279:Administration, Cutaneous; D000577:Amides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems; D057809:HEK293 Cells; D006801:Humans; D008239:Lysine / Q000008:administration & dosage / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D010539:Permeability / Q000187:drug effects; D000077212:Ropivacaine; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D012869:Skin Absorption; D013501:Surface-Active Agents / Q000008:administration & dosage* / Q000737:chemistry*; D013552:Swine; D013748:Tetracaine / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D001672:Biocompatible Materials; D013501:Surface-Active Agents; D013748:Tetracaine; D000077212:Ropivacaine; D008239:Lysine
keywords: Chemical permeation enhancers; Cytotoxicity; Dermal drug delivery; Molecular dynamic simulation; Ropivacaine; Tetracaine