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Development of a pH-sensitive polymer using poly(aspartic acid-graft-imidazole)-block-poly(ethylene glycol) for acidic pH targeting systems

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Abstract

pH sensitive polymer systems can be utilized as smart nanocarriers to deliver hydrophobic drugs specifically to solid tumors or to acidosis-affected rheumatic joints. In this study, a poly(L-aspartic acid-graftimidazole)-block-poly(ethylene glycol) (P(Asp-g-Im)-PEG) block copolymer was synthesized as a pH sensitive nanocarrier targeting acidic pH environments. The polypeptide P(Asp), which was used as a backbone for the hydrophobic block, was synthesized by ring opening polymerization with N-carboxylanhydride (NCA) of β-benzyl-aspartic acid. PEG was included as the hydrophilic block and the polymer was functionalized with imidazole groups to confer pH sensitivity. The prepared P(Asp-g-Im)-PEG is zwitterionic with a pI 6.5; 60% of the available carboxyl groups of P(Asp)-PEG were substituted by imidazole groups. Furthermore, the potentiometric titration curve of P(Asp-g-Im)-PEG demonstrated a broad buffer zone. The micelles prepared from P(Asp-g-Im)-PEG showed pH dependent critical micelle concentrations (CMC), particle sizes, zeta potentials, and morphologies.

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References

  1. T. J. Deming, Prog. Polym. Sci., 32, 858 (2007).

    Article  CAS  Google Scholar 

  2. G. S. Kwon, M. Naito, K. Kataoka, and M. Yokoyama, Colloids Surf. B: Biointerfaces, 2, 429 (1994).

    Article  CAS  Google Scholar 

  3. E. R. Welsh and D. A. Tirrell, Biomacromolecules, 1, 23 (2000).

    Article  CAS  Google Scholar 

  4. K. Kataoka, A. Harada, and Y. Nagasaki, Adv. Drug Deliv. Rev., 47, 113 (2001).

    Article  CAS  Google Scholar 

  5. A. Lavasanifar, J. Samuel, and G. S. Kwon, Adv. Drug Deliv. Rev., 54, 169 (2002).

    Article  CAS  Google Scholar 

  6. K.T. Oh and E. S. Lee, Polym. Adv. Technol., 19, 1907 (2008).

    Article  CAS  Google Scholar 

  7. D. A. Herold, K. Keil, and D. E. Bruns, Biochem. Pharmacol., 38, 73 (1989).

    Article  CAS  Google Scholar 

  8. C. Allen, D. Maysinger, and A. Eisenberg, Colloids Surf. B: Biointerfaces, 16, 3 (1999).

    Article  CAS  Google Scholar 

  9. R. J. Hunter, Foundations of Colloid Science, Oxford University Press, New York, 1991.

    Google Scholar 

  10. K. Osada, R. J. Christie, and K. Kataoka, Journal of The Royal Society Interface, 6, S325 (2009).

    Article  CAS  Google Scholar 

  11. J. M. Anderson, K. L. Spilizewski, and A. Hiltner, in Biocompatibility of Tissue Analogs, D. F. Williams, Ed., CRC Press, Boca Raton, 1985.

    Google Scholar 

  12. G. Gaucher, M.-H. Dufresne, V. P. Sant, N. Kang, D. Maysinger, and J.-C. Leroux, J. Control. Release, 109, 169 (2005).

    Article  CAS  Google Scholar 

  13. M. Yuan and X. Deng, Eur. Polym. J., 37, 1907 (2001).

    Article  CAS  Google Scholar 

  14. H. R. Kricheldorf, α-Aminoacid-N-carboxyanhydrides and related materials, Springer, New York, 1987.

    Google Scholar 

  15. G. Pratesi, G. Savi, and G. Pezzoni, Bri. J. Cancer, 52, 841 (1985).

    Article  CAS  Google Scholar 

  16. M. Yokoyama, M. Miyauchi, N. Yamada, T. Okano, Y. Sakurai, K. Kataoka, and S. Inoue, Cancer Res., 50, 1693 (1990).

    CAS  Google Scholar 

  17. Y. Bae, W.-D. Jang, N. Nishiyama, S. Fukushima, and K. Kataoka, Mol. Biosyst., 1, 242 (2005).

    Article  CAS  Google Scholar 

  18. Y. Bae, N. Nishiyama, S. Fukushima, H. Koyama, M. Yasuhiro, and K. Kataoka, Bioconjug. Chem., 16, 122 (2005).

    Article  CAS  Google Scholar 

  19. E. S. Lee, K. Na, and Y. H. Bae, J. Control. Release, 91, 103 (2003).

    Article  CAS  Google Scholar 

  20. E. S. Lee, K. Na, and Y. H. Bae, Nano Lett., 5, 325 (2005).

    Article  CAS  Google Scholar 

  21. E. S. Lee, K. Na, and Y. H. Bae, J. Control. Release, 103, 405 (2005).

    Article  CAS  Google Scholar 

  22. E. S. Lee, K. T. Oh, D. Kim, Y. S. You, and Y. H. Bae, J. Control. Release, 123, 19 (2007).

    Article  CAS  Google Scholar 

  23. E. S. Lee, H. J. Shin, K. Na, and Y. H. Bae, J. Control. Release, 90, 363 (2003).

    Article  CAS  Google Scholar 

  24. D. Kim, E. S. Lee, K. T. Oh, Z. G. Gao, and Y. H. Bae, Small, 4, 2043 (2008).

    Article  CAS  Google Scholar 

  25. G. M. Kim, Y. H. Bae, and W. H. Jo, Macromol. Biosci., 5, 1118 (2005).

    Article  CAS  Google Scholar 

  26. E. Cesaroni, M. Scarpelli, N. Zamponi, G. Polonara, and M. Zeviani, Pediatr. Neurol., 41, 131 (2009).

    Article  Google Scholar 

  27. M. Ferrari, Nat. Rev. Cancer, 5, 161 (2005).

    Article  CAS  Google Scholar 

  28. D. B. Leeper, et al., Int. J. Radiat. Oncol. Biol. Phys., 28, 935 (1994).

    Article  CAS  Google Scholar 

  29. E. Paleolog and R. Fava, Springer Seminars in Immunopathology, 20, 73 (1998).

    Article  CAS  Google Scholar 

  30. A. Patchornik, A. Berger, and E. Katchalski, J. Am. Chem. Soc., 79, 5227 (1957).

    Article  CAS  Google Scholar 

  31. K. G. Myun, B. Y. Han, and J. W. Ho, Macromol. Biosci., 5, 1118 (2005).

    Article  Google Scholar 

  32. S. Zalipsky and G. Barany, J. Bioact. Compat. Polym., 5, 227 (1990).

    Article  CAS  Google Scholar 

  33. E. A. Lysenko, T. K. Bronich, E. V. Slonkina, A. Eisenberg, V. A. Kabanov, and A. V. Kabanov, Macromolecules, 35, 6351 (2002).

    Article  CAS  Google Scholar 

  34. G. Kwon, M. Naito, M. Yokoyama, T. Okano, Y. Sakurai, and K. Kataoka, Langmuir, 9, 945 (1993).

    Article  CAS  Google Scholar 

  35. G. S. Kwon and T. Okano, Adv. Drug Deliv. Rev., 21, 107 (1996).

    Article  CAS  Google Scholar 

  36. G. Mohajer, E. Lee, and Y. Bae, Pharmaceut. Res., 24, 1618 (2007).

    Article  CAS  Google Scholar 

  37. B. R. Lee, K. T. Oh, H. J. Baik, Y. S. Youn, and E. S. Lee, Int. J. Pharm., 392, 78 (2010).

    Article  CAS  Google Scholar 

  38. N. Kanayama, S. Fukushima, N. Nishiyama, K. Itaka, W.-D. Jang, K. Miyata, Y. Yamasak, U.-I. Chung, and K. Kataok, Chem. Med. Chem., 1, 439 (2006).

    CAS  Google Scholar 

  39. Y. Liu and T. M. Reineke, Bioconjug. Chem., 18, 19 (2006).

    Article  Google Scholar 

  40. A. V. Kabanov, I. R. Nazarova, I. V. Astafieva, E. V. Batrakova, V. Y. Alakhov, A. A. Yaroslavov, and V. A. Kabanov, Macromolecules, 28, 2303 (1995).

    Article  CAS  Google Scholar 

  41. M. Wilhelm, C. L. Zhao, Y. Wang, R. Xu, M. A. Winnik, J. L. Mura, G. Riess, and M. D. Croucher, Macromolecules, 24, 1033 (1991).

    Article  CAS  Google Scholar 

  42. S. Pal and S. P. Moulik, J. Lipid. Res., 24, 1281 (1983).

    CAS  Google Scholar 

  43. K. T. Oh, et al., Int. J. Mol. Sci., 10, 3776 (2009).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. College of Pharmacy, Chung-Ang University, Seoul, 156-756, Korea

    Ji Hoon Kim, Kyung Soo Lee, Jeong Min Yun, Byung Tae Park & Kyung Taek Oh

  2. Department of Diagnostic Radiology and Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, 120-752, Korea

    Young Taik Oh

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  1. Ji Hoon Kim
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  2. Young Taik Oh
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  3. Kyung Soo Lee
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  4. Jeong Min Yun
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  6. Kyung Taek Oh
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Correspondence to Kyung Taek Oh.

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These authors equally contributed to this work.

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Kim, J.H., Oh, Y.T., Lee, K.S. et al. Development of a pH-sensitive polymer using poly(aspartic acid-graft-imidazole)-block-poly(ethylene glycol) for acidic pH targeting systems. Macromol. Res. 19, 453–460 (2011). https://doi.org/10.1007/s13233-011-0502-z

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  • DOI: https://doi.org/10.1007/s13233-011-0502-z

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