title: NO Exchange for a Water Molecule Favorably Changes Iontophoretic Release of Ruthenium Complexes to the Skin.
abstract: Ruthenium (Ru) complexes have been studied as promising anticancer agents. Ru nitrosyl complex (Ru-NO) is one which acts as a pro-drug for the release of nitric oxide (NO). The Ru-aqueous complex formed by the exchange of NO for a water molecule after NO release could also possess therapeutic effects. This study evaluates the influence of iontophoresis on enhancing the skin penetration of Ru-NO and Ru-aqueous and assesses its applicability as a tool in treating diverse skin diseases. Passive and iontophoretic (0.5 mA·cm-2) skin permeation of the complexes were performed for 4 h. The amount of Ru and NO in the stratum corneum (SC), viable epidermis (VE), and receptor solution was quantified while the influence of iontophoresis and irradiation on NO release from Ru-NO complex was also evaluated. Iontophoresis increased the amount of Ru-NO and Ru-aqueous recovered from the receptor solution by 15 and 400 times, respectively, as compared to passive permeation. Iontophoresis produced a higher accumulation of Ru-aqueous in the skin layers as compared to Ru-NO. At least 50% of Ru-NO penetrated theSCwas stable after 4 h. The presence of Ru-NO in this skin layer suggests that further controlled release of NO can be achieved by photo-stimulation after iontophoresis.
authors.affiliation: School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-903, SP, Brazil. danicristine@hotmail.com.|Department of Pharmaceutical Sciences, Federal University of Pernambuco, Recife 50670-901, PE, Brazil. danicristine@hotmail.com.
authors.forename: Danielle C A S
authors.initials: DC
authors.lastname: de Santana
authors.affiliation: School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-903, SP, Brazil. kadias@usp.br.
authors.forename: Karina
authors.initials: K
authors.lastname: Dias
authors.affiliation: School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-903, SP, Brazil. joelgsouza82@gmail.com.
authors.forename: Joel G
authors.initials: JG
authors.lastname: Souza
authors.affiliation: School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-903, SP, Brazil. togunjimi@usp.br.|Department of Pharmaceutics, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife 220282, Osun State, Nigeria. togunjimi@usp.br.
authors.forename: Abayomi T
authors.initials: AT
authors.lastname: Ogunjimi
authors.affiliation: School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-903, SP, Brazil. marinacs@fcfrp.usp.br.
authors.forename: Marina C
authors.initials: MC
authors.lastname: Souza
authors.affiliation: School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-903, SP, Brazil. silva@usp.br.
authors.forename: Roberto S
authors.initials: RS
authors.lastname: Silva
authors.affiliation: School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-903, SP, Brazil. rvianna@fcfrp.usp.br.
authors.forename: Renata F V
authors.initials: RF
authors.lastname: Lopez
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000379:methods*; D004817:Epidermis / Q000378:metabolism*; D007478:Iontophoresis / Q000379:methods*; D009569:Nitric Oxide / Q000737:chemistry*; D010539:Permeability; D011355:Prodrugs / Q000494:pharmacology*; D012428:Ruthenium / Q000737:chemistry*; D012869:Skin Absorption / Q000187:drug effects*; D012871:Skin Diseases / Q000188:drug therapy; D013552:Swine; D014867:Water / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D011355:Prodrugs; D014867:Water; D009569:Nitric Oxide; D012428:Ruthenium
keywords: in vitro skin penetration; iontophoresis; nitric oxide; ruthenium complex