Pharmaceutical Research

, Volume 13, Issue 11, pp 1642–1646 | Cite as

Effect of Non-Ionic Surfactants on the Formation of DNA/Emulsion Complexes and Emulsion-Mediated Gene Transfer

  • Feng Liu
  • Jingping Yang
  • Leaf Huang
  • Dexi Liu
Article

Abstract

Purpose. To study the structure-function relationship of non-ionic surfactants in emulsion-mediated gene delivery.

Methods. Four different types of non-ionic surfactants including Tween, Span, Brij and pluronic copolymers were used as co-emulsifiers for preparation of emulsions composed of Castor oil, dioleoylphosphatidylethanolamine (DOPE) and 3β[N-(N′, N′-dimethylaminoethane) carbamoyl] cholesterol (DC-Chol). The effect of different surfactants on the formation of DNA/emulsion complexes and transfection activity were analyzed using plasmid DNA containing luciferase cDNA as a reporter gene.

Results. Non-ionic surfactants containing branched polyoxyethylene chains as the hydrophilic head group were more effective in preventing the formation of large DNA/emulsion complexes than those containing one or no polyoxyethylene chain. All emulsion formulations except those containing Brij 700 exhibited high activity in transfecting mouse BL-6 cells in the absence of serum. In the presence of serum, however, transfection activity of each formulation varied significantly. Emulsions containing Tween, Brij 72, pluronic F68 and F127 demonstrated increased activity in transfecting cells in the presence of 20% serum. In contrast to emulsions containing Span, long chain polyoxyethylene of Brij showed decreased transfection activity. The particle size of the DNA/emulsion complexes and their ability to transfect cells are dependent on the concentration of non-ionic surfactant in the formulation.

Conclusions. The structure of the hydrophilic head group of the non-ionic surfactants in the emulsion is important in determining how DNA molecules interact with emulsions and the extent to which DNA is transferred inside the cell.

emulsions gene transfer transfection gene therapy non-ionic surfactant cationic lipid 

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REFERENCES

  1. 1.
    P. L. Felgner, and G. M. Ringod. Nature 337:387–388 (1989).Google Scholar
  2. 2.
    J. P. Behr, B. Demeneix, J. P. Loeffler, and J. Perez-Mutual. Proc. Natl. Acad. Sci. USA. 86:6982–6986 (1989).Google Scholar
  3. 3.
    X. Gao and L. Huang. Gene Ther. 2:710–722 (1996).Google Scholar
  4. 4.
    J. H. Felgner, R. Kumar, C. N. Sridhar, C. J. Wheeler., Y. J. Tsai, R. Border, P. Ramsey, M. Martin, and P. L. Felgner. J. Biol. Chem. 269:2550–2561 (1994).Google Scholar
  5. 5.
    H. Farhood, N. Serbina, and L. Huang. Biochim Biophys Acta. 1235:289–295 (1995).Google Scholar
  6. 6.
    X. Zhou and L. Huang. Biochem. Biophys. Acta 1189:195–203 (1994).Google Scholar
  7. 7.
    I. Wrobel and D. Collins. Biochim. Biophys. Acta 1235:296–304 (1995).Google Scholar
  8. 8.
    N. Zhu, D. Liggitt, Y. Liu, and R. Debs. Science 261:209–211 (1993).Google Scholar
  9. 9.
    E. G. Nabel, D. Gordon, Z. Y. Yang, L. Xu, H. San, G. E. Plautz, B. Y. Wu, X. Gao, L. Huang, and G. J. Nabel. Hum. Gene Ther. 3:649–656 (1992).Google Scholar
  10. 10.
    P. L. Felgner, T. R. Gadek, M. Holm, R. Roman, H. W. Chan, M. Wenz, J. P. Northrop, G. M. Ringold, and M. Danielson. Proc. Natl. Acad. Sci. USA 84:7413–7417 (1987).Google Scholar
  11. 11.
    X. Gao and L. Huang. Biochem. Biophys. Res. Comm. 179:280–285 (1991).Google Scholar
  12. 12.
    F. Liu, J. Young, L. Huang, and D. Liu. Pharm. Res. in press.Google Scholar
  13. 13.
    J. Sambrook, E. F. Fritsch, and T. Maniatis. Molecular Cloning: A laboratory Mannual, Cold Spring Harbor Laboratory Press. New York. 1989, Vol. 1, 21–24.Google Scholar

Copyright information

© Plenum Publishing Corporation 1996

Authors and Affiliations

  • Feng Liu
    • 1
  • Jingping Yang
    • 2
  • Leaf Huang
    • 2
  • Dexi Liu
    • 1
  1. 1.Department of Pharmaceutical Sciences, School of PharmacyUniversity of PittsburghPittsburgh
  2. 2.Department of Pharmacology, School of MedicineUniversity of PittsburghPittsburgh

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