Archives of Pharmacal Research

, Volume 31, Issue 1, pp 96–102

Poly(L-lactic acid)/polyethylenimine nanoparticles as plasmid DNA carriers

Article

Abstract

Non-viral vectors such as liposomes, polycations, and nanoparticles have been used as gene delivery systems. In this study, we prepared and characterized biodegradable poly(L-lactic acid) (PLA)/polyethylenimine (PEI) nanoparticles as gene carriers. pCMV/β-gal and pEGFP-C1 were utilized as model plasmid DNAs (pDNA). Nanoparticles were prepared using a double emulsion-solvent evaporation technique, and their pDNA binding capacity was assessed by agarose gel electrophoresis. Transfection was studied in HEK 293 and HeLa cell lines, and the transfection efficiencies were determined by β-galactosidase assay or flow cytometry. Three kinds of PLA/PEI systems were studied by varying the molecular weight of PEI. The PLA/PEI 25K system had a higher transfection efficiency than the PLA/PEI 0.8K or PLA/PEI 750K systems. The transfection efficiency was found to be dependent on the ratio of PLA/PEI nanoparticles to pDNA with an optimum ratio of 60:1 (w/w). The cytotoxicity was dependent on the quantity of PLA/PEI nanoparticles used, but it was comparable to that of commercial Lipofectin™. These results demonstrate the potential of PLA/PEI nanoparticles as gene carriers.

Key words

Nanoparticles Poly(L-lactic acid) Polyethylenimine Transfection Non-viral gene delivery 

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References

  1. Bivas-Benita, M., Romeijn, S., Junginger, H. E., and Borchard, G., PLGA-PEI nanoparticles for gene delivery to pulmonary epithelium. Eur. J. Pharm. Biopharm., 58, 1–6 (2004).PubMedCrossRefGoogle Scholar
  2. Brown, M. D., Schätzlein, A. G., and Uchegbu, I. F., Gene delivery with synthetic (non viral) carriers. Int. J. Pharm., 229, 1–21 (2001).PubMedCrossRefGoogle Scholar
  3. Choi, Y. H., Liu, F., Kim, J. S., Choi, Y. K., Park, J. S., and Kim, S. W., Polyethylene glycol grafted poly-L-lysine as polymeric gene carrier. J. Control. Release, 54, 39–48 (1998).PubMedCrossRefGoogle Scholar
  4. Gebhart, C. L. and Kabanov, A. V., Evaluation of polyplexes as gene transfer agents. J. Control. Release, 73, 401–416 (2001).PubMedCrossRefGoogle Scholar
  5. Godbey, W. T., Wu, K. K., and Mikos, A. G., Poly(ethylenimine) and its role in gene delivery. J. Control. Release, 60, 149–160 (1999).PubMedCrossRefGoogle Scholar
  6. Hirosue, S., Muller, B. G., Mulligan, R. C., and Langer, R., Plasmid DNA encapsulation and release from solvent diffusion nanospheres. J. Control. Release, 70, 231–242 (2001).PubMedCrossRefGoogle Scholar
  7. Kabanov, A. V., Lemieux, P., Vinogradov, S., and Alakahaov V., Pluronic block copolymers: novel functional molecules for gene therapy. Adv. Drug Deliv. Rev., 54, 223–233 (2002).PubMedCrossRefGoogle Scholar
  8. Kakizawa, Y. and Kataoka, K., Block copolymer micelles for delivery of gene and related compounds. Adv. Drug Deliv. Rev., 54, 203–222 (2002).PubMedCrossRefGoogle Scholar
  9. Kim, I. S., Lee, S. K., Park, Y. M., Lee, Y. B., Shin, S. C., Lee, K. C., and Oh, I. J., Physicochemical characterization of pol(L-lactic acid) and poly(D,L-lactide-co-glycolide) nanoparticles with polyethylenimine as gene delivery carrier. Int. J. Pharm., 298, 255–262 (2005).PubMedCrossRefGoogle Scholar
  10. Kim, J. S., Kim, B. I., Maruyama, A., Akaike, T., and Kim, S. W., A new non-viral DNA delivery vector: the terplex system. J. Control. Release, 53, 175–182 (1998).PubMedCrossRefGoogle Scholar
  11. Kircheis, R., Wightman, L., and Wagner, E., Design and gene delivery activity of modified polyethylenimine. Adv. Drug Deliv. Rev., 53, 341–358 (2001).PubMedCrossRefGoogle Scholar
  12. Leong, K. W., Mao, H. Q., Truong-Le, V. L., Roy, K., Walsh, S. M., and August, J. T., DNA polycation nanospheres as nonviral gene delivery vehicles. J. Control. Release, 53, 183–193 (1998).PubMedCrossRefGoogle Scholar
  13. Lobenberg, R., Araujo, L., and Kreuter, J., Body distribution of azidothymidine bound to nanoparticles after oral administration. Eur. J. Pharm. Biopharm., 44, 127–132 (1997).CrossRefGoogle Scholar
  14. Maruyama, A., Ishihara, T., Kim, J. S., Kim, S. W., and Akaike, T., Nanoparticle DNA carrier with poly(L-lysine) grafted polysaccharide copolymer and poly(D,L-lactic acid). Bioconjugate Chem., 8, 735–742 (1997).CrossRefGoogle Scholar
  15. Panyam, J. and Labhasetwar, V., Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv. Drug Deliv. Rev., 55, 329–347 (2003).PubMedCrossRefGoogle Scholar
  16. Perez, C., Sanchez, D., Putnam, D., Ting, D., Langer, R., and Alonso, M. J., Poly(lactic acid)-poly(ethylene glycol) nanoparticles as new carriers for the delivery of plasmid DNA. J. Control. Release, 75, 211–224 (2001).PubMedCrossRefGoogle Scholar
  17. Prabha, S., Zhou, W. Z., Panyam, J., and Labhasetwar, V., Size-dependency of nanoparticle-mediated gene transfection: studies with fractionated nanoparticles. Int. J. Pharm., 244, 105–115 (2002).PubMedCrossRefGoogle Scholar
  18. Ravi-Kumar, M. N. V., Bakowsky, U., and Lehr, C. M., Preparation and characterization of cationic PLGA nanospheres as DNA carriers. Biomaterials, 25, 1771–1777 (2004).PubMedCrossRefGoogle Scholar
  19. Rhaese, S., Briesen, H. V., Rubsamen-Waigmann, H., Kreuter, J., and Langer, K., Human serum albumin-polyethylenimine nanoparticles for gene delivery. J. Control. Release, 92, 199–208 (2003).PubMedCrossRefGoogle Scholar
  20. Tiyaboonchai, W., Woiszwillo, J., and Middaugh, R., Formulation and characterization of DNA-polyethylenimine-dextran sulfate nanoparticles. Eur. J. Pharm. Sci., 19, 191–202 (2003).PubMedCrossRefGoogle Scholar
  21. Zambaux, M. F., Bonneaux, F., Gref, R., Maincent, P., Dellacherie, E., Alonso, M. J., Labrude, P., and Vigneron, C., Influence of experimental parameters on the characteristics of poly(lactic acid) nanoparticles prepared by a double emulsion method. J. Control. Release, 50, 31–40 (1998).PubMedCrossRefGoogle Scholar
  22. Zheng, J., Manuel, W. S., and Hornsby, P. J., Transfection of cells mediated by biodegradable polymer materials with surface-bound polyethylenimine. Biotechnol. Prog., 16, 254–257 (2000).PubMedCrossRefGoogle Scholar

Copyright information

© The Pharmaceutical Society of Korea 2008

Authors and Affiliations

  1. 1.College of MedicineChonnam National UniversityGwangjuKorea
  2. 2.College of Pharmacy and Research Institute of Drug Development, and Nanotechnology Research CenterChonnam National UniversityGwangjuKorea

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