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Drug Release and Targeting: the Versatility of Polymethacrylate Nanoparticles for Peroral Administration Revealed by Using an Optimized In Vitro-Toolbox

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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.

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Abbreviations

API:

Active pharmaceutical ingredient

CLSM:

Confocal laser scanning microscopy

COX-2:

Cyclooxygenase-2

DAPI:

4′,6-Diamidin-2-phenylindol

DMEM:

Dulbecco’s Modified Eagle Medium

FCS:

Fetal calf serum

GI:

Gastrointestinal

mTHPC:

Meso-tetrakis(3-hydroxyphenyl)chlorin

MWCO:

Molecular weight cut-off

PBS:

Phosphate buffered saline

PCS:

Photon correlation spectroscopy

PDI:

Polydispersity index

PTFE:

Polytetrafluoroethylene

rpm:

Rotations per minute

SD:

Standard deviation

SEM:

Scanning electron microscopy

TEM:

Transmission electron microscopy

WST:

Water soluble tetrazolium

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ACKNOWLEDGMENTS AND DISCLOSURES

This work has been supported by the Else Kröner-Fresenius Foundation (EKFS), Research Training Group Translational Research Innovation—Pharma (TRIP). Moreover, the authors acknowledge LOEWE initiative of the State of Hessen for financial support to the Research Center for Translational Medicine and Pharmacology. The analytical part of this work was supported by the DFG (German Research Association) grant SFB1039 Z01. The authors want to acknowledge Prof. Jennifer B. Dressman and Prof. Dieter Steinhilber for their support.

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Authors and Affiliations

  1. Institute of Pharmaceutical Technology, Goethe University, Max-von-Laue-Str. 9, 60438, Frankfurt (Main), Germany

    Susanne Beyer & Matthias G. Wacker

  2. Department of Bioprocess Technologies & Nanotechnology, Fraunhofer Institute for Biomedical Engineering, Ensheimer Straße 48, 66386, St. Ingbert, Germany

    Aline Moosmann & Sylvia Wagner

  3. Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Max-von-Laue-Str. 9, 60438, Frankfurt (Main), Germany

    Astrid S. Kahnt

  4. Fraunhofer Institute of Molecular Biology and Applied Ecology, Project Group for Translational Medicine and Pharmacology, Theodor-Stern-Kai 7, 60596, Frankfurt (Main), Germany

    Thomas Ulshöfer & Michael J. Parnham

  5. Institute of Clinical Pharmacology, Goethe University Hospital, Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany

    Nerea Ferreirós

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  1. Susanne Beyer
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Correspondence to Matthias G. Wacker.

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Beyer, S., Moosmann, A., Kahnt, A.S. et al. Drug Release and Targeting: the Versatility of Polymethacrylate Nanoparticles for Peroral Administration Revealed by Using an Optimized In Vitro-Toolbox. Pharm Res 32, 3986–3998 (2015). https://doi.org/10.1007/s11095-015-1759-2

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  • DOI: https://doi.org/10.1007/s11095-015-1759-2

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