title: In Vitro and In Vivo Evaluation of DMSO and Azone as Penetration Enhancers for Cutaneous Application of Celecoxib.
abstract: Celecoxib (CXB) has been explored as an anti-inflammatory or chemopreventive drug for topical treatment of skin diseases and cancer.
  
  
  
  The main aim of this work was to investigate the potential of dimethylsufoxide (DMSO) and Azone (AZ) as penetration enhancers (P.Es) for topical delivery of CXB.
  
  
  
  The in vitro studies, drug release, skin permeability and potential cytotoxicity/genotoxicity were carried out with formulations containing or not DMSO or AZ (5% and 10%). Skin irritation in rabbits and topical anti-inflammatory activity in mice were assayed in vivo.
  
  
  
  Skin permeation was minimal while higher retention in stratum corneum (SC) and epidermis plus dermis was found (28.0 and 3-fold respectively) from 10.0% AZ compared to the control indicating a localized CXB effect. CXB associated to 5% or 10% DMSO has shown high drug permeation through skin with low retention. Associations of CXB with both enhancers were not cytotoxic or genotoxic, suggesting safety for cutaneous application. In vivo skin irritation assays of all formulations indicated mild irritation effects and, thus, possible use for longer periods. In vivo anti-inflammatory tests showed that ear edema could be inhibited by CXB associated with 5.0% DMSO (53.0%) or 10.0% AZ (40.0%). These inhibition values were almost 2-fold higher when compared to a commercial formula.
  
  
  
  Although DMSO- associated CXB is an efficient edema inhibitor its high skin permeation suggests risks of systemic effects, whereas association to 10% AZ may improve topical delivery of the drug with good anti-inflammatory activity and no cytotoxic/genotoxic or significant skin irritation effects.
authors.affiliation: School of Pharmacy, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho 373, 21.941.902, Rio de Janeiro, RJ, Brazil
authors.forename: Thassia D´Arc
authors.initials: TD
authors.lastname: Senna
authors.affiliation: School of Pharmacy, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho 373, 21.941.902, Rio de Janeiro, RJ, Brazil
authors.forename: Hilton Antonio
authors.initials: HA
authors.lastname: Mata Dos Santos
authors.affiliation: School of Pharmacy, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho 373, 21.941.902, Rio de Janeiro, RJ, Brazil
authors.forename: Daniel Mabundu
authors.initials: DM
authors.lastname: Kibwila
authors.affiliation: Biophysics Institute, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho 373, 21.941.902, Rio de
  Janeiro, RJ, Brazil
authors.forename: Alvaro Costa
authors.initials: AC
authors.lastname: Leitao
authors.affiliation: School of Pharmacy, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho 373, 21.941.902, Rio de Janeiro, RJ, Brazil
authors.forename: Alexandre Dos
authors.initials: AD
authors.lastname: Santos Pyrrho
authors.affiliation: School of Pharmacy, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho 373, 21.941.902, Rio de Janeiro, RJ, Brazil
authors.forename: Marcelo
authors.initials: M
authors.lastname: de Padula
authors.affiliation: Applied Pharmacology Laboratory, Fiocruz, Rua Sizenando Nabuco no 100, Rio de Janeiro, RJ –
  Brasil, 21. 041.250
authors.forename: Elaine Cruz
authors.initials: EC
authors.lastname: Rosas
authors.affiliation: Applied Pharmacology Laboratory, Fiocruz, Rua Sizenando Nabuco no 100, Rio de Janeiro, RJ –
  Brasil, 21. 041.250
authors.forename: Tatiana Almeida
authors.initials: TA
authors.lastname: Padua
authors.affiliation: School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Café, s/n,
  14040-160, Ribeirão Preto, SP, Brazil
authors.forename: Marilisa Guimaraes
authors.initials: MG
authors.lastname: Lara
authors.affiliation: School of Pharmacy, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho 373, 21.941.902, Rio de Janeiro, RJ, Brazil
authors.forename: Maria Bernadete
authors.initials: MB
authors.lastname: Riemma Pierre
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001381:Azepines / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D000068579:Celecoxib / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D004121:Dimethyl Sulfoxide / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D004487:Edema / Q000188:drug therapy; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests; D011817:Rabbits; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D023422:Skin Irritancy Tests; D013552:Swine
chemical_list: D001381:Azepines; D052246:Cyclooxygenase 2 Inhibitors; C035229:laurocapram; D000068579:Celecoxib; D004121:Dimethyl Sulfoxide
keywords: Anti-inflammatory activity; azone; celecoxib; cutaneous permeability; dimethylsulfoxide; glycerol; topical application