Skip to main content
SpringerLink
Log in

Low Potential Ocular Irritation of Arginine-Based Gemini Surfactants and Their Mixtures with Nonionic and Zwitterionic Surfactants

  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Purpose. The aim of this study was to find new biocompatible surfactants and mixtures with low ocular irritant action for application in pharmaceutical formulations and to establish a relationship between their structure and their potential ocular irritant activity.

Methods. An alternative method to the Draize in vivo test, based on the adverse effects of surfactants on the cytoplasmic membrane of red blood cell, was used to evaluate the potential ocular irritation of the surfactants.

Results. It was found that the hemolytic activity of arginine-based gemini surfactants increased with the aliphatic alkyl chain lengths of the hydrophobic tail. The addition of the surfactant with an alkyl chain length of 10 carbon atoms to cocoamidopropilbetaina (TB), decylglucoside (APG), and Nα-lauroyl-arginine ethyl ester (LAE) increases the hemolytic activity moderately for the mixtures with TB and LAE (1.1- and 1.5-fold, respectively) and strongly for APG (fivefold).

Conclusions. The new arginine-based gemini surfactants constitute a suitable alternative to commercial surfactants because of their natural origins, which make them biocompatible and renewable products. Based on their hemolytic activity as an alternative to the Draize test, these new arginine-based gemini surfactants and their mixtures can be classified as mild irritants. This fact constitutes an advantage, especially for pharmaceutical and cosmetic applications.

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. M. Paulsson and K. Edsman. Controlled drug release from gels using surfactants aggregates. II Vesicles formed from mixtures of amphiphilic drugs and oppositely charged surfactants. Pharm. Res. 18:1586-1592 (2001).

    Google Scholar 

  2. P. Clapés and M. R. Infante. Amino acid-based surfactants: Enzymatic synthesis, properties and potential applications. Biocat. Biotrans 20:215-233 (2002).

    Google Scholar 

  3. R. Valivety, I. S. Gill, and E. N. Vulfson. Application of enzymes to the synthesis of amino acid-based bola and gemini surfactants. J. Surfactants Deterg 1:177-185 (1998).

    Google Scholar 

  4. J. D. Hines. Theoretical aspects of micellisation in surfactant mixtures. Curr. Op. Coll. Interf. Sci. 6:350-356 (2001).

    Google Scholar 

  5. W. J. W. Pape, U. Pfannenbecker, and U. Hoppe. Validation of the red blood cell test system as in vitro assay for the rapid screening of irritation potential of surfactants. Mol. Toxicol. 1:525-536 (1987).

    Google Scholar 

  6. J. H. Draize, G. Woodard, and H. O. Calvery. Methods for the study of irritation and toxicity of substances applied to the skin and mucous membranes. J. Pharmacol. Exp. Ther. 82:377-390 (1944).

    Google Scholar 

  7. M. Balls, P. A. Botham, L. H. Bruner, and H. Spielmann. The EC/HO international validation study on alternatives to the Draize eye irritation test. Toxicol. In Vitro 9:871-929 (1995).

    Google Scholar 

  8. A. A. Kulkarni and A. J. Hopfinger. Membrane-interaction QSAR analysis: application to the estimation of eye irritation by organic compounds. Pharm. Res. 16:1245-1253 (1999).

    Google Scholar 

  9. B. Isomaa, H. Hägerstrand, G. Paatero, and A. C. Engbliom. Permeability alterations and antihemolysis induced by amphiphiles in human erythrocytes. Biochim Biophys Acta. 860:510-524 (1986).

    Google Scholar 

  10. E. Piera, M. R. Infante, and P. Clapes. Chemo-enzymatic synthesis of arginine-based gemini surfactants. Biotechnol. Bioeng. 70:323-331 (2000).

    Google Scholar 

  11. M. R. Infante, J. Seguer, A. Pinazo, and M. P. Vinardell. Synthesis and properties of symmetrical nonionic double chain surfactants from lysine. J. Dispers. Sci. Technol. 20:621-642 (1999).

    Google Scholar 

  12. M. A. Vives, M. R. Infante, E. García, C. Selve, M. Maugras, and M. P. Vinardell. Erythrocyte hemolysis and shape changes induced by new lysine-derivate surfactants. Chemico-Biol Interact 118:1-18 (1999).

    Google Scholar 

  13. D. Liechtenberg, R. J. Robson, and E. A. Dennis. Solubilization of phospholipids by detergents: structural and kinetic aspects. Biochim. Biophys. Acta 737:285-304 (1983).

    Google Scholar 

  14. M. Macián, J. Seguer, M. R. Infante, C. Selve, and M. P. Vinardell. Preliminary studies of the toxic effects of non-ionic surfactants derived from lysine. Toxicol 106:1-9 (1996).

    Google Scholar 

  15. T. Reinhart and K. H. Bauer. Investigations about hemolysis and solubilization behaviour of nonionic polymeric surfactants. Pharmazie 50:403-407 (1995).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dept. Fisiologia-Divisió IV, Facultat de Farmacia (UB), Av Joan XXIII, s/n, 08028, Barcelona, Spain

    Montserrat Mitjans, Verónica Martínez & M. Pilar Vinardell

  2. Dept. Química de Péptidos y Proteína, IIQA-CSIC, Jorge Girona, Barcelona, Spain

    Pere Clapés

  3. Dept. Tecnología de Tensiactivos, IIQA-CSIC, Jorge Girona, Barcelona, Spain

    Lourdes Pérez & M. Rosa Infante

Authors
  1. Montserrat Mitjans
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Verónica Martínez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pere Clapés
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lourdes Pérez
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Rosa Infante
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. Pilar Vinardell
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Pilar Vinardell.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mitjans, M., Martínez, V., Clapés, P. et al. Low Potential Ocular Irritation of Arginine-Based Gemini Surfactants and Their Mixtures with Nonionic and Zwitterionic Surfactants. Pharm Res 20, 1697–1701 (2003). https://doi.org/10.1023/A:1026164123938

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1026164123938

Search

Navigation