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Journal for Biophysical Chemistry

Sustained release of complexed DNA from films: Study of bioactivity and intracellular tracking


Sustained DNA delivery from polymeric films provides a means for localized and prolonged gene therapy. However, in the case of bioactive molecules such as plasmid DNA (pDNA), there are limitations on the achievable release profiles as well as on the maintenance of bioactivity over time. In this report, the authors have investigated the bioactivity of the released DNA (naked and complexed with lipofectamine) from polymeric films using in vitro cell transfection of COS-7 cell lines. The polymeric system consists of a biodegradable semicrystalline polymer such as poly(ε-caprolactone) (PCL) with or without blended gelatin. Sustained release of lipoplexes and of pDNA is shown over several days. However, lipoplexes released from pure PCL films show no transfection on day 18, whereas lipoplexes released from PCL-gelatin films continue to transfect cells on day 18 of release. Confocal studies were used to determine the reasons for this difference in transfection efficiency, and it is proposed that association of the lipoplex with gelatin confers protection from degradation in the cytoplasm. The results also showed that the bioactivity of released lipoplexes was superior to that of the naked pDNA. For both naked pDNA and the lipoplexes, the presence of gelatin helped to maintain the bioactivity over several days.


  1. 1

    Y. S. Jong, J. Controlled Release 47, 123 (1997).

    CAS  Article  Google Scholar 

  2. 2

    V. Labhasetwar, J. Bonadio, A. S. Goldstein, W. Chen, and R. J. Levy, J. Pharm. Sci. 87, 1347 (1998).

    CAS  Article  Google Scholar 

  3. 3

    D. Luo, K. Woodrow-Mumford, N. Belcheva, and W. M. Saltzman, Pharm. Res. 16, 1300 (1999).

    CAS  Article  Google Scholar 

  4. 4

    Y. Ramgopal, D. Mondal, S. S. Venkatraman, and W. T. Godbey, J. Biomed. Mater. Res. Part B: Appl Biomater. 85B, 496 (2008).

    CAS  Article  Google Scholar 

  5. 5

    Y. Ramgopal, D. Mondal, S. S. Venkatraman, W. T. Godbey, and G. Y. Yuen, J. Biomed. Mater. Res., Part B: Appl. Biomater. 89B, 439 (2009).

    CAS  Article  Google Scholar 

  6. 6

    J. Kohn and R. Langer, in Biomaterials Science, edited by B. Ratner, A. Hoffman, F. Schoen, and J. Lemons (Academic, San Diego, 1996), pp. 64–72.

    Google Scholar 

  7. 7

    J. M. Pachence and J. Kohn, in Principles of Tissue Engineering, edited by R. Lanza, R. Langer, and V. Joseph (Academic, San Diego, 1997), pp. 273–294.

    Google Scholar 

  8. 8

    J. C. Middleton and A. J. Tipton, Biomaterials 21, 2335 (2000).

    CAS  Article  Google Scholar 

  9. 9

    H. Nishida and Y. Tokiwa, J. Environ. Polym. Degrad. 1, 227 (1993).

    CAS  Article  Google Scholar 

  10. 10

    H. Nishida and Y. Tokiwa, Chem. Lett. 1994, 1293 (1994).

    Article  Google Scholar 

  11. 11

    K. Fukushima, C. Abbate, D. Tabuani, M. Gennari, P. Rizzarelli, and G. Camino, Mater. Sci. Eng., C 30, 566 (2010).

    CAS  Article  Google Scholar 

  12. 12

    M. Hakkarainen, Adv. Polym. Sci. 157, 113 (2002).

    CAS  Article  Google Scholar 

  13. 13

    Y. Tabata and Y. Ikada, Adv. Drug Delivery Rev. 31, 287 (1998).

    CAS  Article  Google Scholar 

  14. 14

    K. Kawai, S. Suzuki, Y. Tabata, Y. Ikada, and Y. Nishimura, Biomaterials 21, 489 (2000).

    CAS  Article  Google Scholar 

  15. 15

    M. Yamamoto, Y. Ikada, and Y. Tabata, J. Biomater. Sci., Polym. Ed. 12, 77 (2001).

    CAS  Article  Google Scholar 

  16. 16

    A. J. Kuijpers, P. B. van Wachem, M. J. van Luyn, J. A. Plantinga, G. H. M. Engbers, J. Krijgsveld, S. A. J. Zaat, J. Dankert, and J. Feijen, J. Biomed. Mater. Res. 51, 136 (2000).

    CAS  Article  Google Scholar 

  17. 17

    C. H. Yao, B. S. Liu, S. H. Hsu, Y. S. Chen, and C. C. Tsai, J. Biomed. Mater. Res. Part A 69A, 709 (2004).

    CAS  Article  Google Scholar 

  18. 18

    S. Ando, D. Putnam, D. W. Pack, and R. Langer, J. Pharm. Sci. 88, 126 1999).

    CAS  Article  Google Scholar 

  19. 19

    K. A. Howard, X. W. Li, S. Somavarapu, J. Singh, N. Green, K. N. Atuaha, Y. Ozsoyc, L. W. Seymourb, and H. O. Alpar, Biochim. Biophys. Acta 1674, 149 (2004).

    CAS  Google Scholar 

  20. 20

    H. Cohen-Sacks, V. Elazar, J. Gao, A. Golomb, H. Adwan, N. Korchov, R. J. Levy, M. R. Berger, and G. Golomb, J. Controlled Release 95, 309 (2004).

    CAS  Article  Google Scholar 

  21. 21

    C. B. Rives, A. Rieux, M. Zelivyanskaya, S. R. Stock, W. L. Lowe, Jr., and L. D. Shea, Biomaterials 30, 394 (2009).

    CAS  Article  Google Scholar 

  22. 22

    G. L. Lukacs, P. Haggie, O. Seksek, D. Lechardeur, N. Freedman, and A. S. Verkman, J. Biol. Chem. 275, 1625 (2000).

    CAS  Article  Google Scholar 

  23. 23

    T. Segura and L. D. Shea, Annu. Rev. Mater. Res. 31, 25 (2001).

    CAS  Article  Google Scholar 

  24. 24

    A. Elouahabi and J. Ruysschaert, Mol. Ther. 11, 336 (2005).

    CAS  Article  Google Scholar 

  25. 25

    S. Brunner, T. Sauer, S. Carotta, M. Cotton, M. Saltik, and E. Wagner, Gene Ther. 7, 401 (2000).

    CAS  Article  Google Scholar 

  26. 26

    K. Goldie and A. Mansoor, J. Pharm. Sci. 94, 184 (2004).

    Google Scholar 

  27. 27

    A. R. Thierry, P. Rabinovich, B. Peng, L. C. Mahan, J. L. Bryant, and R. C. Gallo, Gene Ther. 4, 226 (1997).

    CAS  Article  Google Scholar 

  28. 28

    S. W. Yi, T. Y. Yune, T. W. Kim, H. Chung, Y. W. Choi, I. C. Kwon, E. B. Lee, and S. Y. Jeong, Pharm. Res. 17, 314 (2000).

    CAS  Article  Google Scholar 

  29. 29

    V. Escriou, C. Ciolina, F. Lacroix, G. Byk, D. Scherman, and P. Wils, Biochim. Biophys. Acta 1368, 276 (1998).

    CAS  Article  Google Scholar 

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Correspondence to Debasish Mondal.

Additional information

This paper is part of an In Focus section on Biointerphase Science in Singapore, sponsored by Bruker Optik Southeast Asia, IMRE, the Provost's Office and School of Materials Science and Engineering of Nanyang Technological University, and Analytical Technologies Pte Ltd.

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Mondal, D., Ramgopal, Y., Tiwari, S.K. et al. Sustained release of complexed DNA from films: Study of bioactivity and intracellular tracking. Biointerphases 5, FA69–FA77 (2010).

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