Language:
English
In:
Pharmaceutical Research, 2015, Vol.32(12), pp.3986-3998
Description:
Byline: Susanne Beyer (1), Aline Moosmann (2), Astrid S. Kahnt (3), Thomas Ulshofer (4), Michael J. Parnham (4), Nerea Ferreiros (5), Sylvia Wagner (2), Matthias G. Wacker (1) Keywords: biorelevant release; Eudragit[R] RS 100; nanoparticles; peroral drug delivery; Ussing chamber 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[R] 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[R]-nanoparticles into cancer cells was demonstrated. A burst release of the nanoparticles implied poor interaction of TMP-001 with Eudragit[R]. 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[+ or -]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. Author Affiliation: (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 Stra[sz]e 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 Article History: Registration Date: 15/07/2015 Received Date: 30/04/2015 Accepted Date: 15/07/2015 Online Date: 28/07/2015
Keywords:
biorelevant release ; Eudragit® RS 100 ; nanoparticles ; peroral drug delivery ; Ussing chamber
ISSN:
0724-8741
E-ISSN:
1573-904X
DOI:
10.1007/s11095-015-1759-2
URL:
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