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Pharmaceutical Research

, Volume 32, Issue 12, pp 3986–3998 | Cite as

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

  • Susanne Beyer
  • Aline Moosmann
  • Astrid S. Kahnt
  • Thomas Ulshöfer
  • Michael J. Parnham
  • Nerea Ferreirós
  • Sylvia Wagner
  • Matthias G. WackerEmail author
Research Paper

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.

KEY WORDS

biorelevant release Eudragit® RS 100 nanoparticles peroral drug delivery Ussing chamber 

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

Notes

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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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Susanne Beyer
    • 1
  • Aline Moosmann
    • 2
  • Astrid S. Kahnt
    • 3
  • Thomas Ulshöfer
    • 4
  • Michael J. Parnham
    • 4
  • Nerea Ferreirós
    • 5
  • Sylvia Wagner
    • 2
  • Matthias G. Wacker
    • 1
    Email author
  1. 1.Institute of Pharmaceutical TechnologyGoethe UniversityFrankfurt (Main)Germany
  2. 2.Department of Bioprocess Technologies & NanotechnologyFraunhofer Institute for Biomedical EngineeringSt. IngbertGermany
  3. 3.Institute of Pharmaceutical ChemistryGoethe University FrankfurtFrankfurt (Main)Germany
  4. 4.Fraunhofer Institute of Molecular Biology and Applied EcologyProject Group for Translational Medicine and PharmacologyFrankfurt (Main)Germany
  5. 5.Institute of Clinical PharmacologyGoethe University HospitalFrankfurt am MainGermany

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