title: Drug Release and Targeting: the Versatility of Polymethacrylate Nanoparticles for Peroral Administration Revealed by Using an Optimized In Vitro-Toolbox.
abstract: OBJECTIVE
  The contribution of permeability and drug release to drug targeting were investigated in the course of development of a nanosized formulation of the anti-inflammatory compound TMP-001, for the local treatment in the gastrointestinal tract.
  
  
  METHODS
  TMP-001 was encapsulated by nanoprecipitation into Eudragit® RS 100. The permeability of these carriers was investigated in an Ussing chamber model and the release rate was determined under biorelevant conditions. Formulation toxicity and particle-cell-interaction were investigated by flow cytometry, fluorescence and electron microscopy. Furthermore, spray drying was performed.
  
  
  RESULTS
  Effective internalization of Eudragit®-nanoparticles into cancer cells was demonstrated. A burst release of the nanoparticles implied poor interaction of TMP-001 with Eudragit®. A sustained release (70.5% release after 30 min compared to 98.0% for the API) was accomplished after spray drying yielded an increased particle size. Recovery rate of TMP-001 after spray drying was 94.2 ± 5.9%.
  
  
  CONCLUSIONS
  The release of API from polymeric nanoparticles contributes profoundly to the in vivo-performance of drug delivery devices in the gastrointestinal tract. The impact of drug-polymer interaction and particle size was analyzed. Sustained release of TMP-001 could only be achieved by increasing particle size. Therefore, biorelevant release testing has been demonstrated to be a valid tool for nanoformulation design.
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.affiliation: Department of Bioprocess Technologies & Nanotechnology, Fraunhofer Institute for Biomedical Engineering, Ensheimer Straße 48, 66386, St. Ingbert, Germany.
authors.forename: Aline
authors.initials: A
authors.lastname: Moosmann
authors.affiliation: Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Max-von-Laue-Str. 9, 60438, Frankfurt (Main), Germany.
authors.forename: Astrid S
authors.initials: AS
authors.lastname: Kahnt
authors.affiliation: Fraunhofer Institute of Molecular Biology and Applied Ecology, Project Group for Translational Medicine and Pharmacology, Theodor-Stern-Kai 7, 60596, Frankfurt (Main), Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ulshöfer
authors.affiliation: Fraunhofer Institute of Molecular Biology and Applied Ecology, Project Group for Translational Medicine and Pharmacology, Theodor-Stern-Kai 7, 60596, Frankfurt (Main), Germany.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Parnham
authors.affiliation: Institute of Clinical Pharmacology, Goethe University Hospital, Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany.
authors.forename: Nerea
authors.initials: N
authors.lastname: Ferreirós
authors.affiliation: Department of Bioprocess Technologies & Nanotechnology, Fraunhofer Institute for Biomedical Engineering, Ensheimer Straße 48, 66386, St. Ingbert, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Wagner
authors.affiliation: Institute of Pharmaceutical Technology, Goethe University, Max-von-Laue-Str. 9, 60438, Frankfurt (Main), Germany. wacker@em.uni-frankfurt.de.
authors.forename: Matthias G
authors.initials: MG
authors.lastname: Wacker
mesh_terms: D000284:Administration, Oral; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D065546:Drug Liberation; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011109:Polymethacrylic Acids / Q000737:chemistry*
chemical_list: D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D004337:Drug Carriers; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer
keywords: Eudragit® RS 100; Ussing chamber; biorelevant release; nanoparticles; peroral drug delivery