Skip to main content
SpringerLink
Log in

Skin Penetration and Mechanisms of Action in the Delivery of the D2-Agonist Rotigotine from Surfactant-Based Elastic Vesicle Formulations

  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Purpose. This study was performed to investigate the effect of elastic and rigid vesicles on the penetration of the D2 dopamine agonist rotigotine across human skin and to further elucidate the mechanisms of action of the elastic vesicles.

Methods. A series of rotigotine-loaded vesicles were prepared, ranging from very elastic to very rigid. The drug penetration from these vesicles across human skin was studied in vitro using flow-through diffusion cells. Micelle and buffer solutions were investigated as controls. For the most elastic vesicle composition, two additional variables were investigated. Coapplication of drug and vesicles was compared to pretreatment, and the effect of the drug entrapment efficiency was investigated.

Results. The very elastic vesicle formulation L-595/PEG-8-L (50/50) gave steady-state fluxes of 214.4 ± 27.8 ng/(h · cm2). This formulation was the most effective formulation and significantly better than the rigid vesicle formulations as well as the micelle and buffer controls. However, coapplication and a high drug entrapment efficiency were essential factors for an optimal drug delivery from elastic vesicle formulations.

Conclusions. Elastic vesicles are promising vehicles for transdermal drug delivery. It is essential that drug molecules are applied together with and entrapped within the vesicles themselves, suggesting that elastic vesicles act as drug carrier systems and not solely as penetration enhancers.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. H. Schreier and J. A. Bouwstra. Liposomes and niosomes as topical drug carriers: dermal and transdermal drug delivery. J. Control. Rel. 30:1-15 (1994).

    Google Scholar 

  2. E. Touitou, H. E. Junginger, N. D. Weiner, and M. Mezei. Liposomes as carriers for topical and transdermal delivery. J. Pharm. Sci. 9:1189-1203 (1992).

    Google Scholar 

  3. G. Cevc, D. Schatzlein, and G. Blume. Transdermal drug carriers: basic properties, optimization and transfer efficiency in the case of epicutaneously applied peptides. J. Control. Rel. 36:3-16 (1995).

    Google Scholar 

  4. G. Cevc. Transfersomes, liposomes and other lipid suspensions on the skin: permeation enhancement, vesicle penetration, and transdermal drug delivery. Crit. Rev. Ther. Drug Carrier Syst. 13:257-388 (1996).

    Google Scholar 

  5. E. Touitou, N. Dayan, L. Bergelson, B. Godin, and M. Eliaz. Ethosomes—novel vesicular carriers for enhanced delivery: characterization and skin penetration properties. J. Control. Rel. 65:403-418 (2000).

    Google Scholar 

  6. G. Cevc, A. Schatzlein, D. Gebauer, and G. Blume. Ultra-high efficiency of drug and peptide transfer through the intact skin by means of novel drug-carriers, Transfersomes. In K. R. Brain, V. J. James, and K. A. Walters (eds), Prediction of Percutaneous Penetration, Volume 3B, STS Publishing, Cardiff, UK, 1993, pp. 226-236.

    Google Scholar 

  7. G. Cevc and G. Blume. Lipid vesicles penetrate into intact skin owing to the transdermal osmotic gradients and hydration force. Biochim. Biophys. Acta 1104:226-232 (1992).

    Google Scholar 

  8. G. Cevc, D. Gebauer, J. Stieber, A. Schatzlein, and G. Blume. Ultraflexible vesicles, Transfersomes, have an extremely low pore penetration resistance and transport therapeutic amounts of insulin across the intact mammalian skin. Biochim. Biophys. Acta 1368:201-215 (1998).

    Google Scholar 

  9. M. E. Planas, P. Gonzalez, L. Rodriguez, S. Sanchez, and G. Cevc. Noninvasive percutaneous induction of topical analgesia by a new type of drug carrier, and prolongation of local pain insensitivity by anesthetic liposomes. Anesth. Analg. 75:615-621 (1992).

    Google Scholar 

  10. G. M. M. El Maghraby, A. C. Williams, and B. W. Barry. Skin delivery of oestradiol from deformable and traditional liposomes: mechanistic studies. J. Pharm. Pharmacol. 51:1123-1134 (1999).

    Google Scholar 

  11. G. M. M. El Maghraby, A. C. Williams, and B. W. Barry. Skin delivery of 5-fluorouracil from ultradeformable and standard liposomes in vitro. J. Pharm. Pharmacol. 53:1069-1077 (2001).

    Google Scholar 

  12. G. M. M. El Maghraby, A. C. Williams, and B. W. Barry. Oestradiol skin delivery from ultradeformable liposomes: refinement of surfactant concentration. Int. J. Pharm. 196:63-74 (2000).

    Google Scholar 

  13. P. L. Honeywell-Nguyen, P. M. Frederik, P. H. H. Bomans, H. E. Junginger, and J. A. Bouwstra. Transdermal delivery of pergolide from surfactant-based elastic and rigid vesicles: characterisation and in vitro transport studies. Pharm. Res. 19:992-998 (2002).

    Google Scholar 

  14. P. L. Honeywell-Nguyen, M. H. van den Bussche, H. E. Junginger, and J. A. Bouwstra. The effect of surfactant-based elastic and rigid vesicles on the penetration of lidocaine across human skin. STP Pharma 12:257-262 (2002).

    Google Scholar 

  15. P. L. Honeywell-Nguyen and J. A. Bouwstra. The in vitro transport of pergolide from surfactant-based elastic vesicles through human skin: a suggested mechanism of action. J. Control. Rel. 86:145-156 (2003).

    Google Scholar 

  16. P. L. Honeywell-Nguyen, A. M. de Graaff, H. W. W. Groenink, and J. A. Bouwstra. The in vivo and in vitro interactions of elastic and rigid vesicles with human skin. Biochim. Biophys. Acta 1573:130-140 (2002).

    Google Scholar 

  17. P. L. Honeywell-Nguyen, H. W. W. Groenink, A. M. de Graaff, and J. A. Bouwstra. The in vivo transport of elastic vesicles into human skin: effects of occlusion, volume and duration of application, J. Control. Rel. (accepted).

  18. P. J. Swart and R. A. de Zeeuw. Pharmacokinetics of the dopamine D2 agonist S(-)-2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin in freely moving rats. J. Pharm. Sci. 82:200-203 (1993).

    Google Scholar 

  19. B. A. I. van den Bergh, P. W. Wertz, H. E. Junginger, and J. A. Bouwstra. Elasticity of vesicles assessed by electron spin resonance, electron microscopy and extrusion measurements. Int. J. Pharm. 217:13-24 (2001).

    Google Scholar 

  20. A. J. Baillie, A. T. Florence, L. R. Hume, G. T. Muirhead, and A. Rogerson. The preparation and properties of niosomes–non-ionic surfactant vesicles. J. Pharm. Pharmacol. 37:863-868 (1985).

    Google Scholar 

  21. B. A. I. van den Bergh, J. Vroom, H. Gerritsen, H. E. Junginger, and J. A. Bouwstra. Interactions of elastic and rigid vesicles with human skin in vitro: electron microscopy and two-photon excitation microscopy. Biochim. Biophys. Acta 1461:155-173 (1999).

    Google Scholar 

  22. G. Cevc and G. Blume. New, highly efficient formulation of diclofenac for the topical transdermal administration in ultradeformable drug carriers, Transfersomes. Biochim. Biophys. Acta 1514:191-205 (2001).

    Google Scholar 

  23. V. P. Calabrese, K. A. Lloyd, P. Brancazio, E. Cefali, P. Martin, J. Wall, Jr., and D. Sica. N-0923, a novel soluble dopamine D2 agonist in the treatment of parkinsonism. Mov. Disord. 13:768-774 (1998).

    Google Scholar 

  24. G. Cevc. A Schatzlein, H. Richardsen. Ultradeformable lipid vesicles can penetrate the skin and other semi-permeable barriers unfragmented. Evidence from double label CLSM experiments and direct size measurements. Biochim. Biophys. Acta 1564:21-30 (2002).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Technology, Leiden/Amsterdam Center for Drug Research, University of Leiden, 2300 RA, Leiden, The Netherlands

    P. Loan Honeywell-Nguyen, Sonia Arenja & Joke A. Bouwstra

Authors
  1. P. Loan Honeywell-Nguyen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sonia Arenja
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joke A. Bouwstra
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joke A. Bouwstra.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Honeywell-Nguyen, P.L., Arenja, S. & Bouwstra, J.A. Skin Penetration and Mechanisms of Action in the Delivery of the D2-Agonist Rotigotine from Surfactant-Based Elastic Vesicle Formulations. Pharm Res 20, 1619–1625 (2003). https://doi.org/10.1023/A:1026191402557

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1026191402557

Search

Navigation