, 1:71 | Cite as

Microencapsulation of nanoparticulate complexes of DNA with cationic lipids and polymers in pectin beads for targeted gene delivery

  • Richard D. Harvey
  • Sandrine Bourgeois
  • Peter Pietzonka
  • Laurent Desire
  • Elias Fattal
Original Article


Nanoparticulate complexes of plasmid DNA (pDNA) with cationic liposomes/polymer, of approx 200 nm diameter, were encapsulated with a high degree of efficiency within calcium pectinate gel beads. Electron microscopy showed the DNA nanocomplexes to be evenly distributed throughout the gel matrix. Controlled release of pDNA-lipid nanocomplexes was achieved by the action of pectinase enzymes, whereas release of naked and polymer-complexed DNA was found to be more greatly influenced by the swelling behavior of the polysaccharide matrices in buffer alone. Physical degradation of pDNA within pectin beads was found to be accelerated during bead drying, most probably as a result of shear forces generated within the gel matrices by the evaporation of water. Plasmid complexation with cationic liposomes provided a greater degree of protection for the DNA during bead drying than complexation with cationic polymer, and was shown to successfully transfect cultured cells after release from the beads, via the action of pectinase. Observations concerning the physical stability of nanocomplexed pDNA, and its encapsulation within and release from pectin gel beads, are discussed with reference to the electrostatic interactions existing between the various components.

Key Words

Calcium pectinate DNA nanocomplexes cationic liposomes polyethylenimine gene delivery 


  1. 1.
    McCormick, F. (1999), Trends Genet. 15, M53-M56.CrossRefGoogle Scholar
  2. 2.
    Midgley, R. and Kerr, D. (1999), Lancet 353, 391–399.CrossRefGoogle Scholar
  3. 3.
    Croyle, M. A., Stone, M., Amidon, G. L., and Roessler, B. J. (1998), Gene Ther. 5, 645–654.CrossRefGoogle Scholar
  4. 4.
    Lau, C., Soriano, H. E., Ledley, F. D., et al. (1995), Hum. Gene Ther. 6, 1145–1151.Google Scholar
  5. 5.
    Westbrook, C. A. and Arenas, R. B. (1995), Adv. Drug Deliv. Rev. 17, 349–355.CrossRefGoogle Scholar
  6. 6.
    El-Aneed, A. (2004), J. Cont. Rel. 94, 1–14.CrossRefGoogle Scholar
  7. 7.
    Fichera, A., Guo, Y., Romero, L., Michelassi, F., and Arenas, R. B. (1997), J. Surg. Res. 69, 188–192.CrossRefGoogle Scholar
  8. 8.
    Lew, J. I., Guo, Y., Kim, R. K., Vargish, L., Michelassi, F., and Arenas, R. B. (2002), J. Gastrointest. Surg. 6, 563–568.CrossRefGoogle Scholar
  9. 9.
    Vandamme, T. F., Lenourry, A., Charrueau, C., and Chaumeil, J. (2002), Carb. Poly. 48, 219–231.CrossRefGoogle Scholar
  10. 10.
    Sinha, V. R. and Kumria, R. (2003), Eur. J. Pharm. Sci. 18, 3–18.CrossRefGoogle Scholar
  11. 11.
    Alexakis, T., Boadi, D. K., Quong, D., et al. (1995), Appl. Biochem. Biotech. 50, 93–106.Google Scholar
  12. 12.
    Quong, D. and Neufeld, R. J. (1998), Biotech. Bioeng. 60, 124–134.CrossRefGoogle Scholar
  13. 13.
    Grant, G. T., Morris, E. R., Rees, D. A., et al. (1973), FEBS Lett. 32, 195–198.CrossRefGoogle Scholar
  14. 14.
    Munjeri, O., Collett, J. H., and Fell, J. T. (1997), Drug Deliv. 4, 207–211.Google Scholar
  15. 15.
    Sriamornsak, P. (1998), Int. J. Pharm. 169, 213–220.CrossRefGoogle Scholar
  16. 16.
    Kim, T. H., Park, Y. H., Kim, K. J., and Cho, C. S. (2003), Int. J. Pharm. 250, 371–383.CrossRefGoogle Scholar
  17. 17.
    Thakur, B. R., Singh, R. K., and Handa, A. K. (1997), Crit. Rev. Food Sci. Nutr. 31, 47–73.CrossRefGoogle Scholar
  18. 18.
    Sriamornsak, P. and Nunthanid, J. (1998), Int. J. Pharm. 160, 207–212.CrossRefGoogle Scholar
  19. 19.
    Walter, E., Moelling, K., Pavlovic, J., and Merkle, H. P. (1999), J. Cont. Rel. 61, 361–374.CrossRefGoogle Scholar
  20. 20.
    Evans, R. K., Xu, Z., Bohannon, K. E., Wang, B., Bruner, M. W., and Volkin, D. B. (2000), J. Pharm. Sci. 89, 76–87.CrossRefGoogle Scholar
  21. 21.
    Middaugh, C. R., Evans, R. K., Montgomery, D. L., and Casimiro, D. R. (1998), J. Pharm. Sci. 87, 130–146.CrossRefGoogle Scholar
  22. 22.
    Lengsfeld, C. S. and Anchordoquy, T. J. (2002), J. Pharm. Sci. 91, 1581–1589.CrossRefGoogle Scholar
  23. 23.
    Friend, D. R. (1991), Adv. Drug Deliv. Rev. 7, 149–199.CrossRefGoogle Scholar
  24. 24.
    Désiré, L., Head, M. W., Fayein, N. A., Coutois, Y., and Jeanny, J.-C. (1998), Dev. Dynam. 212, 63–74.CrossRefGoogle Scholar
  25. 25.
    Ando, S., Putnam, D., Pack, D. W., and Langer, R. (1999), J. Pharm. Sci. 88, 126–130.CrossRefGoogle Scholar
  26. 26.
    Ho, J. and Neufeld, R. J. (2001), S.T.P.Pharma. Sci. 11, 109–115.Google Scholar
  27. 27.
    Pina, B., Hache, R. J., Arnemann, J., Chalepakis, G., Slater, E. P., and Beato, M. (1990), Mol. Cell Biol. 10, 625–633.Google Scholar
  28. 28.
    Mumper, R. J. and Rolland, A. P. (1998), Adv. Drug Deliv. Rev. 30, 151–172.CrossRefGoogle Scholar
  29. 29.
    Russel, A. D. (2003), Sci. Prog. 86, 115–137.CrossRefGoogle Scholar
  30. 30.
    Kasyanenko, N. A., Bartoshevich, S. F., and Frisman, E. V. (1986), Mol. Biol. 19, 1136–1142.Google Scholar
  31. 31.
    Lindahl, T. (1993), Nature 362, 709–715.CrossRefGoogle Scholar
  32. 32.
    Albersheim, P. (1959), Biochem. Biophys. Res. Commun. 1, 253–256.CrossRefGoogle Scholar
  33. 33.
    Levy, M. S., Collins, I. J., Yim, S. S., et al. (1999), Bioproc. Eng. 20, 7–13.CrossRefGoogle Scholar
  34. 34.
    Radler, J. O., Koltover, I., Salditt, T., and Safinya, C. R. (1997), Science 275, 810–814.CrossRefGoogle Scholar
  35. 35.
    Sriamornsak, P. (1999), Eur. J. Pharm. Sci. 8, 221–227.CrossRefGoogle Scholar
  36. 36.
    Scherer, G. W. (1990), J. Non-Cryst. Solids 121, 104–109.CrossRefGoogle Scholar
  37. 37.
    Caddock, B. D. and Hull, D. (2002), J. Mat. Sci. 37, 825–834.CrossRefGoogle Scholar
  38. 38.
    Cummings, J. H., Southgate, D. A. T., Branch, W. J., et al. (1979), Br. J. Nutr. 41, 477–485.CrossRefGoogle Scholar
  39. 39.
    Liu, L. S., Fishman, M. L., Kost, J., and Hicks, K. B. (2003), Biomaterials 24, 3333–3343.CrossRefGoogle Scholar
  40. 40.
    Arigita, C., Zuidam, N. J., Crommelin, D. J. A., and Hennink, W. E. (1999), Pharm. Res. 16, 1534–1541.CrossRefGoogle Scholar
  41. 41.
    Quong, D., Yeo, J.-N., and Neufeld, R. J. (1999), J. Microencapsul. 16, 73–82.CrossRefGoogle Scholar
  42. 42.
    Kenaway, E. R. and Sakran, M. A. (1996), Ind. Eng. Chem. Res. 35, 3726–3729.CrossRefGoogle Scholar

Copyright information

© Humana Press Inc 2005

Authors and Affiliations

  • Richard D. Harvey
    • 1
  • Sandrine Bourgeois
    • 1
  • Peter Pietzonka
    • 1
  • Laurent Desire
    • 1
  • Elias Fattal
    • 1
  1. 1.Centre d’Etudes Pharmaceutiques, CNRS UMR 8612Université Paris-SudChâtenay-MalabryFrance

Personalised recommendations