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Sustained release of complexed DNA from films: Study of bioactivity and intracellular tracking
Biointerphases volume 5, pages FA69–FA77 (2010)
Abstract
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.
Reference
Y. S. Jong, J. Controlled Release 47, 123 (1997).
V. Labhasetwar, J. Bonadio, A. S. Goldstein, W. Chen, and R. J. Levy, J. Pharm. Sci. 87, 1347 (1998).
D. Luo, K. Woodrow-Mumford, N. Belcheva, and W. M. Saltzman, Pharm. Res. 16, 1300 (1999).
Y. Ramgopal, D. Mondal, S. S. Venkatraman, and W. T. Godbey, J. Biomed. Mater. Res. Part B: Appl Biomater. 85B, 496 (2008).
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).
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.
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.
J. C. Middleton and A. J. Tipton, Biomaterials 21, 2335 (2000).
H. Nishida and Y. Tokiwa, J. Environ. Polym. Degrad. 1, 227 (1993).
H. Nishida and Y. Tokiwa, Chem. Lett. 1994, 1293 (1994).
K. Fukushima, C. Abbate, D. Tabuani, M. Gennari, P. Rizzarelli, and G. Camino, Mater. Sci. Eng., C 30, 566 (2010).
M. Hakkarainen, Adv. Polym. Sci. 157, 113 (2002).
Y. Tabata and Y. Ikada, Adv. Drug Delivery Rev. 31, 287 (1998).
K. Kawai, S. Suzuki, Y. Tabata, Y. Ikada, and Y. Nishimura, Biomaterials 21, 489 (2000).
M. Yamamoto, Y. Ikada, and Y. Tabata, J. Biomater. Sci., Polym. Ed. 12, 77 (2001).
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).
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).
S. Ando, D. Putnam, D. W. Pack, and R. Langer, J. Pharm. Sci. 88, 126 1999).
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).
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).
C. B. Rives, A. Rieux, M. Zelivyanskaya, S. R. Stock, W. L. Lowe, Jr., and L. D. Shea, Biomaterials 30, 394 (2009).
G. L. Lukacs, P. Haggie, O. Seksek, D. Lechardeur, N. Freedman, and A. S. Verkman, J. Biol. Chem. 275, 1625 (2000).
T. Segura and L. D. Shea, Annu. Rev. Mater. Res. 31, 25 (2001).
A. Elouahabi and J. Ruysschaert, Mol. Ther. 11, 336 (2005).
S. Brunner, T. Sauer, S. Carotta, M. Cotton, M. Saltik, and E. Wagner, Gene Ther. 7, 401 (2000).
K. Goldie and A. Mansoor, J. Pharm. Sci. 94, 184 (2004).
A. R. Thierry, P. Rabinovich, B. Peng, L. C. Mahan, J. L. Bryant, and R. C. Gallo, Gene Ther. 4, 226 (1997).
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).
V. Escriou, C. Ciolina, F. Lacroix, G. Byk, D. Scherman, and P. Wils, Biochim. Biophys. Acta 1368, 276 (1998).
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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). https://doi.org/10.1116/1.3493692
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DOI: https://doi.org/10.1116/1.3493692