Susanne Beyer1, Aline Moosmann2, Astrid S Kahnt3, Thomas Ulshöfer4, Michael J Parnham4, Nerea Ferreirós5, Sylvia Wagner2, Matthias G Wacker6. 1. Institute of Pharmaceutical Technology, Goethe University, Max-von-Laue-Str. 9, 60438, Frankfurt (Main), Germany. 2. Department of Bioprocess Technologies & Nanotechnology, Fraunhofer Institute for Biomedical Engineering, Ensheimer Straße 48, 66386, St. Ingbert, Germany. 3. Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Max-von-Laue-Str. 9, 60438, Frankfurt (Main), Germany. 4. Fraunhofer Institute of Molecular Biology and Applied Ecology, Project Group for Translational Medicine and Pharmacology, Theodor-Stern-Kai 7, 60596, Frankfurt (Main), Germany. 5. Institute of Clinical Pharmacology, Goethe University Hospital, Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany. 6. Institute of Pharmaceutical Technology, Goethe University, Max-von-Laue-Str. 9, 60438, Frankfurt (Main), Germany. wacker@em.uni-frankfurt.de.
Abstract
PURPOSE: 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%. CONCLUSION: 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.
PURPOSE: 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%. CONCLUSION: 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: Anne des Rieux; Eva G E Ragnarsson; Elisabet Gullberg; Véronique Préat; Yves-Jacques Schneider; Per Artursson Journal: Eur J Pharm Sci Date: 2005 Jul-Aug Impact factor: 4.384
Authors: Stephanie E A Gratton; Patricia A Ropp; Patrick D Pohlhaus; J Christopher Luft; Victoria J Madden; Mary E Napier; Joseph M DeSimone Journal: Proc Natl Acad Sci U S A Date: 2008-08-12 Impact factor: 11.205
Authors: J B Dressman; R R Berardi; G H Elta; T M Gray; P A Montgomery; H S Lau; K L Pelekoudas; G J Szpunar; J G Wagner Journal: Pharm Res Date: 1992-07 Impact factor: 4.200