title: Cubosome dispersions as delivery systems for percutaneous administration of indomethacin.
abstract: OBJECTIVE
  The present study concerns the production and characterization of monooleine (MO) dispersions as drug delivery systems for indomethacin, taken as model anti-inflammatory drug.
  
  
  METHODS
  Dispersions were produced by emulsification and homogenization of MO and poloxamer in water. Morphology and dimensional distribution of the disperse phase have been characterized by cryo-transmission electron microscopy and photon correlation spectroscopy, respectively. X-ray diffraction has been performed to determine the structural organization of the disperse phase. Sedimentation field flow fractionation (SdFFF) has been performed to investigate drug distribution in the dispersion. An in vitro diffusion study was conducted by Franz cell associated to stratum corneum epidermis membrane on cubosome dispersions viscosized by carbomer. In vivo studies based on skin reflectance spectrophotometry and tape stripping were performed to better investigate the performance of cubosome as indomethacin delivery system.
  
  
  RESULTS
  Microscopy studies showed the coexistence of vesicles and cubosomes. X-ray diffraction revealed the presence of a bicontinuous cubic phase of spatial symmetry Im3m (Q229). SdFFF demonstrated that no free drug was present in the dispersion. Indomethacin incorporated in viscosized MO dispersions exhibited a lower flux with respect to the analogous formulation containing the free drug in the aqueous phase and to the control formulation based on carbomer gel. Reflectance spectroscopy demonstrated that indomethacin incorporated into MO dispersions can be released in a prolonged fashion. Tape-stripping experiments corroborated this finding.
  
  
  CONCLUSIONS
  MO dispersions can be proposed as nanoparticulate systems able to control the percutaneous absorption of indomethacin.
authors.affiliation: Dipartmento di Scienze Farmaceutiche, Universitá di Ferrara, Via Fossato di Mortara, 19, 44100 Ferrara, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Esposito
authors.forename: Rita
authors.initials: R
authors.lastname: Cortesi
authors.forename: Markus
authors.initials: M
authors.lastname: Drechsler
authors.forename: Lydia
authors.initials: L
authors.lastname: Paccamiccio
authors.forename: Paolo
authors.initials: P
authors.lastname: Mariani
authors.forename: Catia
authors.initials: C
authors.lastname: Contado
authors.forename: Elisa
authors.initials: E
authors.lastname: Stellin
authors.forename: Enea
authors.initials: E
authors.lastname: Menegatti
authors.forename: Francesco
authors.initials: F
authors.lastname: Bonina
authors.forename: Carmelo
authors.initials: C
authors.lastname: Puglia
mesh_terms: D000328:Adult; D000465:Algorithms; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D020285:Cryoelectron Microscopy; D015194:Diffusion Chambers, Culture; D016503:Drug Delivery Systems; D004355:Drug Stability; D004890:Erythema / Q000188:drug therapy; D005260:Female; D031521:Fractionation, Field Flow; D005989:Glycerides / Q000737:chemistry; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D008297:Male; D010316:Particle Size; D011832:Radiation Injuries / Q000188:drug therapy; D012867:Skin / Q000473:pathology; D012869:Skin Absorption; D012995:Solubility; D014461:Ultracentrifugation; D014466:Ultraviolet Rays; D014783:Viscosity; D014961:X-Ray Diffraction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005989:Glycerides; D007213:Indomethacin