title: In vitro and in vivo influence of penetration enhancers in the topical application of celecoxib.
abstract: OBJECTIVE
  We investigated the potential effects of oleic acid (OA) and glycerol monooleate (GMO) on the skin delivery of CXB.
  
  
  METHODS
  The influence of both OA and GMO (5.0% or 10.0%) on the in vitro skin permeability of CXB (2.0%) was evaluated using propylene glycol (PG) as a vehicle. Also the in vitro potential cytotoxicity and genotoxicity and in vivo assays (skin irritation in rabbits and topical anti-inflammatory activity by in mice) were conducted.
  
  
  RESULTS
  As expected, the amount of CXB that permeated through the skin was minimal, but drug retention on the viable skin (epidermis plus dermis) was higher in association with treatment with 5.0% OA or GMO compared to the control treatment, meaning that there was a localized effect of CXB in the skin. No formulation presented cytotoxic or genotoxic potential, suggesting safety for cutaneous application. In vivo skin irritation assays indicated that no formulation was irritating to the skin becomes its use possible for a prolonged time. In vivo anti-inflammatory experiments indicated that both edema and protein extravasation were inhibited with a maximum % inhibition of 53.5.0% and 61.0% for 5.0 % GMO, respectively, and 48.0% and 35.5% for 5.0% OA, respectively. Such formulations were able to inhibit around twofold the percentage of ear edema in mice compared to a commercial product reference diclofenac commercial formula.
  
  
  CONCLUSIONS
  There is no topical formulation currently available that contains both CXB and 5.0% GMO or OA, suggesting them as potential adjuvants that improve the skin delivery of CXB.
authors.affiliation: School of Pharmacy, Federal University of Rio de Janeiro , Rio de Janeiro, RJ , Brazil .
authors.forename: Oliesia Gonzalez
authors.initials: OG
authors.lastname: Quiñones
authors.forename: Hilton Antonio
authors.initials: HA
authors.lastname: Mata dos Santos
authors.forename: Daniel Mabundu
authors.initials: DM
authors.lastname: Kibwila
authors.forename: Alvaro
authors.initials: A
authors.lastname: Leitão
authors.forename: Alexandre
authors.initials: A
authors.lastname: dos Santos Pyrrho
authors.forename: Marcelo de
authors.initials: Md
authors.lastname: Pádula
authors.forename: Elaine Cruz
authors.initials: EC
authors.lastname: Rosas
authors.forename: Marilisa Guimarães
authors.initials: MG
authors.lastname: Lara
authors.forename: Maria Bernadete Riemma
authors.initials: MB
authors.lastname: Pierre
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry; D000068579:Celecoxib; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004487:Edema / Q000188:drug therapy; D005989:Glycerides / Q000737:chemistry; D008297:Male; D051379:Mice; D019301:Oleic Acid / Q000737:chemistry; D010539:Permeability; D019946:Propylene Glycol / Q000737:chemistry; D011720:Pyrazoles / Q000008:administration & dosage* / Q000737:chemistry*; D011817:Rabbits; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption / Q000502:physiology; D013449:Sulfonamides / Q000008:administration & dosage* / Q000737:chemistry*; D013552:Swine
chemical_list: D000893:Anti-Inflammatory Agents; D005989:Glycerides; D011720:Pyrazoles; D013449:Sulfonamides; D019301:Oleic Acid; D019946:Propylene Glycol; C005953:monoolein; D000068579:Celecoxib
keywords: Anti-inflammatory activity; celecoxib; cutaneous permeability; glycerol monooleate; oleic acid; topical application