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Synthesis and Characterization of a Hydroxylated Dendrimeric Gene Delivery Carrier

  • Kim, Tae-Il (School of Chemistry & Molecular Engineering, Seoul National University) ;
  • Bai, Cheng-Zhe (School of Chemistry & Molecular Engineering, Seoul National University) ;
  • Park, Jong-Sang (School of Chemistry & Molecular Engineering, Seoul National University)
  • Published : 2007.08.20

Abstract

Arginine conjugated PAMAM dendrimer, PAMAM-R was modified with propylene oxide via hydroxylation of primary amines of arginine residues. About 49 amines were detected to be converted to amino alcohols by 1H NMR. The newly synthesized polymer, PAMAM-R-PO was able to completely retard pDNA from a charge ratio of 2. The average diameter of PAMAM-R-PO polyplex was found to be 242 nm at a charge ratio of 30. The Zeta-potential value of PAMAM-R-PO polyplex was able to reach 20-30 mV over a charge ratio of 10. PAMAM-R-PO indicated higher cell viability than unmodified PAMAM-R on HeLa and 293 cells because of its hydroxylated amines. Transfection experiments on 293 cells showed that the transfection efficiency of PAMAM-R-PO was found to be 1.5-1.9 times higher than that of PEI25kDa at a charge ratio of 30. The polymer eventually displayed about 2 times greater transfection efficiency than PAMAM-R at the same charge ratio in the absence of serum. Therefore, we concluded that the modification of primary amines of PAMAMR to amino alcohols gives positive effects such as reduced cytotoxicity and enhanced transfection efficiency on 293 cells for gene delivery potency of PAMAM-R.

Keywords

References

  1. Luo, D.; Saltzman, W. M. Nat. Biotechnol. 2000, 18, 33 https://doi.org/10.1038/71889
  2. Zauner, W.; Ogris, M.; Wagner, E. Adv. Drug Del. Rev. 1998, 30, 97 https://doi.org/10.1016/S0169-409X(97)00110-5
  3. Veena, V.; Thomas, T.; Thomas, T. J. Biochemistry 2002, 41, 14085 https://doi.org/10.1021/bi0203987
  4. Kim, T.-i.; Seo, H. J.; Baek, J.-u.; Park, J.-H.; Park, J.-S. Bull. Korean Chem. Soc. 2005, 26, 175 https://doi.org/10.1007/s11814-009-0029-6
  5. Svenson, S.; Tomalia, D. A. Adv. Drug Del. Rev. 2005, 57, 2106 https://doi.org/10.1016/j.addr.2005.09.018
  6. Dufes, C.; Uchegbu, I. F.; Schatzlein, A. G. Adv. Drug Del. Rev. 2005, 57, 2177 https://doi.org/10.1016/j.addr.2005.09.017
  7. Gillies, E. R.; Frechet, J. M. J. Drug Discov. Today 2005, 10, 35 https://doi.org/10.1016/S1359-6446(04)03276-3
  8. Patri, A. K.; Majoros, I. J.; Baker, J. R. Jr. Curr. Opin. Chem. Biol. 2002, 6, 466 https://doi.org/10.1016/S1367-5931(02)00347-2
  9. Kim, T.-i.; Baek, J.-u.; Bai, C. Z.; Park, J.-s. Bull. Korean Chem. Soc. 2006, 27, 1894 https://doi.org/10.5012/bkcs.2006.27.11.1894
  10. Esfand, R.; Tomalia, D. A. Drug Discov. Today 2001, 6, 427 https://doi.org/10.1016/S1359-6446(01)01757-3
  11. Luo, D.; Haverstick, K.; Belcheva, N.; Han, E.; Saltzman, W. M. Macromolecules 2002, 35, 3456 https://doi.org/10.1021/ma0106346
  12. Kim, T.-i.; Seo, H. J.; Choi, J. S.; Jang, H.-S.; Baek, J.-u.; Kim, K.; Park, J.-S. Biomacromolecules 2004, 5, 2487 https://doi.org/10.1021/bm049563j
  13. Choi, J. S.; Ko, K. S.; Park, J. S.; Kim, Y.-H.; Kim, S. W.; Lee, M. Int. J. Pharm. 2006, 320, 171 https://doi.org/10.1016/j.ijpharm.2006.05.002
  14. Wada, K.; Arima, H.; Tsutsumi, T.; Chihara, Y.; Hattori, K.; Hirayama, F.; Uekama, K. J. Control Release 2005, 104, 397 https://doi.org/10.1016/j.jconrel.2005.02.016
  15. Choi, J. S.; Nam, K.; Park, J.-y.; Kim, J.-B.; Lee, J.-K.; Park, J.-s. J. Control Release 2004, 99, 445 https://doi.org/10.1016/j.jconrel.2004.07.027
  16. Tziveleka, L.-A.; Psarra, A.-M. G.; Tsiourvas, D.; Paleos, C. M. J. Control Release 2007, 117, 137 https://doi.org/10.1016/j.jconrel.2006.10.019
  17. Lee, M. J.; Cho, S. S.; You, J. R.; Lee, Y.; Kang, B. D.; Choi, J. S.; Park, J.-W.; Suh, Y.-L.; Kim, J.-A.; Kim, D.-K.; Park, J.-S. Gene Ther. 2002, 9, 859
  18. Mahato, R. I.; Rolland, A.; Tomlinson, E. Pharm. Res. 1997, 14, 853 https://doi.org/10.1023/A:1012187414126

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