Pharmaceutical Research

, Volume 34, Issue 6, pp 1171–1179 | Cite as

Combination of SEDDS and Preactivated Thiomer Technology: Incorporation of a Preactivated Thiolated Amphiphilic Polymer into Self-Emulsifying Delivery Systems

  • Gergely Hetényi
  • Janine Griesser
  • Isabelle Nardin
  • Andreas Bernkop-Schnürch
Research Paper
First Online:
Received:
Accepted:

Abstract

Purpose

The aim of the study was to create novel mucoadhesive drug delivery systems by incorporating amphiphilic hydrophobically modified, thiolated and preactivated polymers (preactivated thiomers) into self-emulsifying drug delivery systems (SEDDS).

Methods

L-Cysteine methyl ester was covalently attached to the polymeric backbone of Pemulen TR-2 and preactivated using 2-mercaptonicotinic acid (2-MNA). These thiomers were incorporated in a concentration of 0.3% (w/v) into SEDDS. The size distribution and the zeta potential of the emulsions were evaluated by dynamic light scattering. Mucoadhesive properties of thiomers-SEDDS spiked with FDA (fluorescein diacetate) were examined utilizing rheological measurement, permeation studies and in vitro residence time study on porcine mucosa. Cell viability tests were additionally performed.

Results

734 ± 58 μmol L-Cysteine methyl ester and 562 ± 71 μmol 2-MNA could be attached per gram polymer of Pemulen TR-2. Emulsions exhibited a droplet size range between 180 and 270 nm. Blank SEDDS possessed a zeta potential value between −5.7 and −8.6 mV, whereas thiomers-SEDDS between −14.6 and −17.2 mV. Viscous modulus of thiomer and preactivated thiomer containing SEDDS-mucus mixture was 8-fold and 11-fold increased in comparison to reference. The amount of FDA permeated the mucus layer was 2-fold lower in case of thiomers-SEDDS compared to blank SEDDS. A prolonged residence time was observed for thiomers-SEDDS over 45 min. During cell viability studies no severe toxic effects were detected.

Conclusion

The novel developed SEDDS with incorporated thiomers might be a promising tool for mucoadhesive oral drug delivery.

Key Words

mucoadhesive drug delivery mucoadhesive SEDDS nanocarrier preactivated thiomer self-emulsifying drug delivery systems 

Abbreviations

DTNB

5,5´-Dithio-bis(2-nitrobenzoic acid

EDAC

1-Ethyl-3-(3- dimethylaminopropyl) carbodiimide hydrochloride

FDA

Fluorescein diacetate

2-MNA

2-Mercaptonicotinic acid

MTT

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

NHS

N-hydroxysuccinimide

SEDDS

Self-emulsifying drug delivery systems

TNBS

2,4,6-Trinitrobenzene sulfonic acid

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Notes

Acknowledgements and Disclosures

The research leading to these results has received funding from the European Community’s Seventh Framework Programme (FP7/2007–2013) under grant agreement n° 280,761.

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Gergely Hetényi
    • 1
  • Janine Griesser
    • 1
  • Isabelle Nardin
    • 1
  • Andreas Bernkop-Schnürch
    • 1
    • 2
  1. 1.Thiomatrix Forschungs-und Beratungs GmbH,InnsbruckAustria
  2. 2.Department of Pharmaceutical Technology, Center for Chemistry and Biomedicine, Institute of PharmacyLeopold-Franzens-UniversityInnsbruckAustria

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