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In Vitro Evaluation of Various Buccal Permeation Enhancing Systems for PACAP (Pituitary Adenylate Cyclase-Activating Polypeptide)

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Purpose

Buccal administration of pituitary adenylate cyclase-activating polypeptide (PACAP) could represent a new possibility for the treatment of type 2 diabetes. In this study the effect of various buccal permeation enhancers on PACAP and FD-4 was evaluated.

Methods

The permeation-enhancing properties of the well-established permeation enhancers sodium deoxycholate (Na DOC) and cetrimide on the permeation of PACAP were investigated on freshly excised porcine buccal mucosa in Ussing chambers. Furthermore, the effect of chitosan and that of chitosan-4-thiobutylamidine conjugate (chitosan–TBA) optionally in combination with reduced glutathione (GSH) on the permeation of PACAP across the buccal mucosa was studied.

Results

The apparent permeability coefficient (P app) of PACAP in buffer only was 5.7 ± 3.1×10−8 cm/s. In the presence of 5% (m/v) Na DOC, the enhancement of the permeation was 18.6-fold, whereas due to the addition of 5% (m/v) cetrimide an enhancement ratio of 46.5 was obtained. In the presence of the chitosan–TBA conjugate (1%), a 38.9-fold increased permeation was achieved, whereas unmodified chitosan (1%) did not show any effect. The combination of chitosan–TBA conjugate (1%) with GSH (2%) led to an increase in P app up to 441.7 ± 89.9×10−8 cm/s, which represents a 77.5-fold improvement. The P app of GSH per se was only 1.0 ± 0.2×10−9 cm/s, showing that GSH remains concentrated on the surface of the buccal mucosa. Results were confirmed by additional permeation studies performed with FD-4 used as hydrophilic macromolecular test compound.

Conclusions

Based on their permeation-enhancing properties, chitosan–TBA conjugates represent a promising tool for the buccal administration of peptide drugs, e.g., PACAP.

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Acknowledgments

This work was supported by Bayer AG, 51368 Leverkusen, Germany. The authors wish to thank Mr. Mayerhofer and co-workers for the supply of buccal mucosa of pigs.

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Authors and Affiliations

  1. ThioMatrix GmbH, Mitterweg 24, A-6020, Innsbruck, Austria

    Nina Langoth

  2. Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold Franzens University Innsbruck, Innrain 52, Josef Möller Haus, A-6020, Innsbruck, Austria

    Andreas Bernkop-Schnürch

  3. Bayer AG, 51368, Leverkusen, Germany

    Peter Kurka

Authors
  1. Nina Langoth
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  2. Andreas Bernkop-Schnürch
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  3. Peter Kurka
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Correspondence to Nina Langoth.

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Langoth, N., Bernkop-Schnürch, A. & Kurka, P. In Vitro Evaluation of Various Buccal Permeation Enhancing Systems for PACAP (Pituitary Adenylate Cyclase-Activating Polypeptide). Pharm Res 22, 2045–2050 (2005). https://doi.org/10.1007/s11095-005-7894-4

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  • DOI: https://doi.org/10.1007/s11095-005-7894-4

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