Development of a pH-Sensitive Polymer Using Poly(aspartic acid-graft-imidazole)-block-Poly(ethylene glycol) for Acidic pH Targeting Systems

Ji Hoon Kim; Young Taik Oh; Kyung Soo Lee; Jeong Min Yun; Byung Tae Park; Kyung Taek Oh

Macromolecular Research, Vol.19, No.5, 453-460, May, 2011

DOI10.1007/s13233-011-0502-z Export Citation

Development of a pH-Sensitive Polymer Using Poly(aspartic acid-graft-imidazole)-block-Poly(ethylene glycol) for Acidic pH Targeting Systems

Ji Hoon Kim, Young Taik Oh¹, Kyung Soo Lee, Jeong Min Yun, Byung Tae Park, and Kyung Taek Oh^†

College of Pharmacy, Chung-Ang University, Seoul, 156-756, Korea
¹Department of Diagnostic Radiology and Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, 120-752, Korea

E-mail:

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.

Keywords:pH sensitive;micelle destabilization;nanocarrier;polyelectrolytes;poly(aspartic acid-graft-imidazole).

[References]

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Kwon GS, Naito M, Kataoka K, Yokoyama M, Colloids Surf. B: Biointerfaces, 2, 429 (1994)
Welsh ER, Tirrell DA, Biomacromolecules, 1(1), 23 (2000)
Kataoka K, Harada A, Nagasaki Y, Adv. Drug Deliv. Rev., 47, 113 (2001)
Lavasanifar A, Samuel J, Kwon GS, Adv. Drug Deliv. Rev., 54, 169 (2002)
Oh KT, Lee ES, Polym. Adv. Technol., 19, 1907 (2008)
Herold DA, Keil K, Bruns DE, Biochem. Pharmacol., 38, 73 (1989)
Allen C, Maysinger D, Eisenberg A, Colloids Surf. B: Biointerfaces, 16, 3 (1999)
Hunter RJ, Foundations of Colloid Science, Oxford University Press, New York,
Osada K, Christie RJ, Kataoka K, J. Royal Society Interface, 6, S325 (2009)
Anderson JM, Spilizewski KL, Hiltner A, in Biocompatibility of Tissue Analogs, Williams DF, Ed., CRC Press, Boca Raton, 1985.
Gaucher G, Dufresne MH, Sant VP, Kang N, Maysinger D, Leroux JC, J. Control. Release, 109, 169 (2005)
Yuan M, Deng X, Eur. Polym. J., 37, 1907 (2001)
Kricheldorf HR, α-Aminoacid-N-carboxyanhydrides and related materials, Springer, New York, 1987.
Pratesi G, Savi G, Pezzoni G, Bri. J. Cancer, 52, 841 (1985)
Yokoyama M, Miyauchi M, Yamada N, Okano T, Sakurai Y, Kataoka K, Inoue S, Cancer Res., 50, 1693 (1990)
Bae Y, Jang WD, Nishiyama N, Fukushima S, Kataoka K, Mol. Biosyst., 1, 242 (2005)
Bae Y, Nishiyama N, Fukushima S, Koyama H, Yasuhiro M, Kataoka K, Bioconjugate Chem., 16, 122 (2005)
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Lee ES, Oh KT, Kim D, You YS, Bae YH, J. Control. Release, 123, 19 (2007)
Lee ES, Shin HJ, Na K, Bae YH, J. Control. Release, 90, 363 (2003)
Kim D, Lee ES, Oh KT, Gao ZG, Bae YH, Small, 4, 2043 (2008)
Kim GM, Bae YH, Jo WH, Macromol. Biosci., 5, 1118 (2005)
Cesaroni E, Scarpelli M, Zamponi N, Polonara G, Zeviani M, Pediatr. Neurol., 41, 131 (2009)
Ferrari M, Nat. Rev. Cancer, 5, 161 (2005)
Leeper DB, et al., Int. J. Radiat. Oncol. Biol. Phys., 28, 935 (1994)
Paleolog E, Fava R, Springer Seminars in Immunopathology, 20, 73 (1998)
Patchornik A, Berger A, Katchalski E, J. Am. Chem. Soc., 79, 5227 (1957)
Myun KG, Han BY, Ho JW, Macromol. Biosci., 5, 1118 (2005)
Zalipsky S, Barany G, J. Bioact. Compat. Polym., 5, 227 (1990)
Lysenko EA, Bronich TK, Slonkina EV, Eisenberg A, Kabanov VA, Kabanov AV, Macromolecules, 35(16), 6351 (2002)
Kwon G, Naito M, Yokoyama M, Okano T, Sakurai Y, Kataoka K, Langmuir, 9, 945 (1993)
Kwon GS, Okano T, Adv. Drug Deliv. Rev., 21, 107 (1996)
Mohajer G, Lee E, Bae Y, Pharm. Res., 24, 1618 (2007)
Lee BR, Oh KT, Baik HJ, Youn YS, Lee ES, Int. J. Pharm., 392, 78 (2010)
Kanayama N, Fukushima S, Nishiyama N, Itaka K, Jang WD, Miyata K, Yamasak Y, Chung UI, Kataok K, Chem. Med. Chem., 1, 439 (2006)
Liu Y, Reineke TM, Bioconjugate Chem., 18, 19 (2006)
Kabanov AV, Nazarova IR, Astafieva IV, Batrakova EV, Alakhov VY, Yaroslavov AA, Kabanov VA, Macromolecules, 28(7), 2303 (1995)
Wilhelm M, Zhao CL, Wang Y, Xu R, Winnik MA, Mura JL, Riess G, Croucher MD, Macromolecules, 24, 1033 (1991)
Pal S, Moulik SP, J. Lipid Res., 24, 1281 (1983)
Oh KT, Baik HJ, Lee AH, Oh YT, Youn YS, Lee ES, Int. J. Mol. Sci., 10(9), 3776 (2009)

[Referenced By]

[1] Deming TJ, Prog. Polym. Sci, 32, 858 (2007)

[2] Kwon GS, Naito M, Kataoka K, Yokoyama M, Colloids Surf. B: Biointerfaces, 2, 429 (1994)

[3] Welsh ER, Tirrell DA, Biomacromolecules, 1(1), 23 (2000)

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

[5] Lavasanifar A, Samuel J, Kwon GS, Adv. Drug Deliv. Rev., 54, 169 (2002)

[6] Oh KT, Lee ES, Polym. Adv. Technol., 19, 1907 (2008)

[7] Herold DA, Keil K, Bruns DE, Biochem. Pharmacol., 38, 73 (1989)

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

[9] Hunter RJ, Foundations of Colloid Science, Oxford University Press, New York,

[10] Osada K, Christie RJ, Kataoka K, J. Royal Society Interface, 6, S325 (2009)

[11] Anderson JM, Spilizewski KL, Hiltner A, in Biocompatibility of Tissue Analogs, Williams DF, Ed., CRC Press, Boca Raton, 1985.

[12] Gaucher G, Dufresne MH, Sant VP, Kang N, Maysinger D, Leroux JC, J. Control. Release, 109, 169 (2005)

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

[14] Kricheldorf HR, α-Aminoacid-N-carboxyanhydrides and related materials, Springer, New York, 1987.

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

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

[17] Bae Y, Jang WD, Nishiyama N, Fukushima S, Kataoka K, Mol. Biosyst., 1, 242 (2005)

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

[19] Lee ES, Na K, Bae YH, J. Control. Release, 91, 103 (2003)

[20] Lee ES, Na K, Bae YH, Nano Lett., 5, 325 (2005)

[21] Lee ES, Na K, Bae YH, J. Control. Release, 103, 405 (2005)

[22] Lee ES, Oh KT, Kim D, You YS, Bae YH, J. Control. Release, 123, 19 (2007)

[23] Lee ES, Shin HJ, Na K, Bae YH, J. Control. Release, 90, 363 (2003)

[24] Kim D, Lee ES, Oh KT, Gao ZG, Bae YH, Small, 4, 2043 (2008)

[25] Kim GM, Bae YH, Jo WH, Macromol. Biosci., 5, 1118 (2005)

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

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

[28] Leeper DB, et al., Int. J. Radiat. Oncol. Biol. Phys., 28, 935 (1994)

[29] Paleolog E, Fava R, Springer Seminars in Immunopathology, 20, 73 (1998)

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

[31] Myun KG, Han BY, Ho JW, Macromol. Biosci., 5, 1118 (2005)

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

[33] Lysenko EA, Bronich TK, Slonkina EV, Eisenberg A, Kabanov VA, Kabanov AV, Macromolecules, 35(16), 6351 (2002)

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

[35] Kwon GS, Okano T, Adv. Drug Deliv. Rev., 21, 107 (1996)

[36] Mohajer G, Lee E, Bae Y, Pharm. Res., 24, 1618 (2007)

[37] Lee BR, Oh KT, Baik HJ, Youn YS, Lee ES, Int. J. Pharm., 392, 78 (2010)

[38] Kanayama N, Fukushima S, Nishiyama N, Itaka K, Jang WD, Miyata K, Yamasak Y, Chung UI, Kataok K, Chem. Med. Chem., 1, 439 (2006)

[39] Liu Y, Reineke TM, Bioconjugate Chem., 18, 19 (2006)

[40] Kabanov AV, Nazarova IR, Astafieva IV, Batrakova EV, Alakhov VY, Yaroslavov AA, Kabanov VA, Macromolecules, 28(7), 2303 (1995)

[41] Wilhelm M, Zhao CL, Wang Y, Xu R, Winnik MA, Mura JL, Riess G, Croucher MD, Macromolecules, 24, 1033 (1991)

[42] Pal S, Moulik SP, J. Lipid Res., 24, 1281 (1983)

[43] Oh KT, Baik HJ, Lee AH, Oh YT, Youn YS, Lee ES, Int. J. Mol. Sci., 10(9), 3776 (2009)