title: Bridging laboratory and large scale production: preparation and in vitro-evaluation of photosensitizer-loaded nanocarrier devices for targeted drug delivery.
abstract: OBJECTIVE
  Industrial production of nanosized drug delivery devices is still an obstacle to the commercialization of nanomedicines. This study encompasses the development of nanoparticles for peroral application in photodynamic therapy, optimization according to the selected product specifications, and the translation into a continuous flow process.
  
  
  METHODS
  Polymeric nanoparticles were prepared by nanoprecipitation of Eudragit® RS 100 in presence and in absence of glycofurol. The photosensitizer temoporfin has been encapsulated into these carrier devices. Process parameters were optimized by means of a Design of Experiments approach and nanoparticles with optimal characteristics were manufactured by using microreactor technology. The efficacy was determined by means of cell culture models in A-253 cells.
  
  
  RESULTS
  Physicochemical properties of nanoparticles achieved by nanoprecipitation from ethanolic solutions were superior to those obtained from a method based upon glycofurol. Nanoencapsulation of temoporfin into the matrix significantly reduced toxicity of this compound, while the efficacy was maintained. The release profiles assured a sustained release at the site of action. Finally, the transfer to continuous flow technology was achieved.
  
  
  CONCLUSIONS
  By adjusting all process parameters, a potent formulation for application in the GI tract was obtained. The essential steps of process development and scale-up were part of this formulation development.
authors.affiliation: Institute of Pharmaceutical Technology,, Goethe University, Max-von-Laue-Str. 9,, 60438, Frankfurt (Main), Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Beyer
authors.forename: Li
authors.initials: L
authors.lastname: Xie
authors.forename: Susanna
authors.initials: S
authors.lastname: Gräfe
authors.forename: Vitali
authors.initials: V
authors.lastname: Vogel
authors.forename: Kerstin
authors.initials: K
authors.lastname: Dietrich
authors.forename: Arno
authors.initials: A
authors.lastname: Wiehe
authors.forename: Volker
authors.initials: V
authors.lastname: Albrecht
authors.forename: Werner
authors.initials: W
authors.lastname: Mäntele
authors.forename: Matthias G
authors.initials: MG
authors.lastname: Wacker
mesh_terms: D002460:Cell Line; D003692:Delayed-Action Preparations / Q000737:chemistry*; D016503:Drug Delivery Systems; D006801:Humans; D008652:Mesoporphyrins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D053758:Nanoparticles / Q000737:chemistry*; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000737:chemistry*
chemical_list: D003692:Delayed-Action Preparations; D008652:Mesoporphyrins; D017319:Photosensitizing Agents; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; D011092:Polyethylene Glycols; C072269:temoporfin; C018557:glycofurol