Preparation of Multifunctional Polymeric Micelles for Antiviral Treatment

Yong Sik Ahn; Hye Jung Baik; Bo Reum Lee; Eun Seong Lee; Kyung Taek Oh; Don Haeng Lee; Yu Seok Youn

Macromolecular Research, Vol.18, No.8, 747-752, August, 2010

DOI10.1007/s13233-010-0802-8 Export Citation

Preparation of Multifunctional Polymeric Micelles for Antiviral Treatment

Yong Sik Ahn, Hye Jung Baik, Bo Reum Lee, Eun Seong Lee^†, Kyung Taek Oh¹, Don Haeng Lee², and Yu Seok Youn³

Division of Biotechnology, The Catholic University of Korea, Gyeonggi-do, 420-743, Korea
¹College of Pharmacy, Chung-Ang University, Seoul, 155-756, Korea
²Department of Internal Medicine, Inha University, Incheon, 402-751, Korea
³College of Pharmacy, Pusan National University, Busan, 609-735, Korea

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In this study, a poly(L-lactic acid)-b-poly(ethylene glycol) (PLLA-b-PEG) diblock copolymer modified with a sialic acid derivative (methyl-b-neuraminic acid: mNA) was prepared for the development and application of a therapeutic nanosystem with multifunctionality. The terminal carboxyl group of PEG was coupled with mNA via N,N’-dicyclohexyl carbodiimide (DCC)-and N-hydroxysuccinimide (NHS)-mediated amide formation. Polymeric micelles were formed using the diafilteration method at pH 7.4, which resulted in a micelle self-assembly with the PLLA block at the core and PEG-mNA block on the shell. An anionic charge was formed on the surface of the micelle at physiological pH (~pH 7.4) due to mNA. Amantadine (AMT), a model drug for antiviral treatment, was loaded into the micellar core. These micelles were expected to exhibit multiple therapeutic activity that originated from the antiviral activity of mNA on the shell and the sustained release of AMT from the micellar core.

Keywords:polymeric micelle;sialic acid;multifunctionality;antiviral

[References]

Jong WHD, Borm P, Int. J. Nanomedicine, 3, 133 (2008)
Oh KT, Lee ES, Kim DI, Bae YH, Int. J. Pharm., 358, 177 (2008)
Zhao S, Lee JH, Macromol. Res., 17(3), 156 (2009)
Shin YM, Lim KS, Jin JY, Jeong SI, Lee YM, Shin H, Kim KS, Macromol. Res., 17(12), 1039 (2009)
Nobs L, Buchegger F, Gurny R, Allemann E, J. Pharm. Sci., 93, 1980 (2004)
Jaracz S, Kuznetsova LV, Ojima I, Bioorg. Med. Chem., 13, 5043 (2005)
Wong JY, Kuhl TL, Israelachvili JN, Mullah N, Zalipsky S, Science, 275(5301), 820 (1997)
Bae MS, Lee KY, Park YJ, Mooney DJ, Macromol. Res., 15(5), 469 (2007)
Kong G, Braun RD, Dewhirst MW, Cancer Res., 60, 4440 (2000)
Lee ES, Gao Z, Bae YH, J. Control. Release, 132, 164 (2008)
Lee ES, Na K, Bae YH, Nano Lett., 5, 325 (2005)
Lee ES, Kim D, Youn YS, Oh KT, Bae YH, Angew. Chem.-Int. Edit., 47, 2418 (2008)
Lee ES, Gao Z, Kim D, Park K, Kwon IC, Bae YH, J. Control. Release, 129, 228 (2008)
Khdair A, Handa H, Mao G, Panyam J, Eur. J. Pharm. Biopharm., 71, 214 (2009)
Wu W, Air GM, Virology, 325, 340 (2004)
Lagana A, Marino A, Fago G, Martinez BP, Anal. Chim. Acta, 306, 65 (1995)
Yamauchi H, Yano T, Kato T, Tanaka I, Nakabayashi S, Higashi K, Miyoshi S, Yamada H, Int. J. Pharm., 113, 141 (1995)
Gregoriadis G, Fernandes A, Mital M, McCormack B, Cell. Mol. Life Sci., 57, 1964 (2000)
Wandinger KR, Hagenah JM, Kluter H, Rothermundt M, Peters M, Vieregge P, J. Neuroimmunol., 98, 214 (1999)
Choi WY, Kim SJ, Lee NJ, Kwon MH, Yang IS, Kim MJ, Cheong SG, Kwon DH, Lee JY, Oh HB, Kang C, Antiviral Res., 84, 199 (2009)
Zalipsky S, Barany G, J. Bioact. Compat. Polym., 5, 227 (1990)
Ranjit V, Munasinghe N, Corrie JET, Kelly G, Martin SR, Biconjugate Chem., 18, 231 (2007)
Darwish IA, Khedr AS, Askal HF, Mahmoud RM, J. Appl. Spectrosc., 73, 792 (2006)
Lee SH, Baek HH, Kim JH, Choi SW, Macromol. Res., 17(12), 1010 (2009)
Lee HJ, Kim SE, Kwon IK, Park C, Kim C, Yang J, Lee SC, Chem. Commun., 46, 377 (2010)
Socha M, Bartecki P, Passirani C, Sapin A, Damge C, Lecompte T, Barre J, El Ghazouani F, Maincent P, J. Drug Target., 17, 575 (2009)
Duek EAR, Zavaglia CAC, Belangero WD, Polymer, 40, 6456 (1999)

[Referenced By]

[1] Jong WHD, Borm P, Int. J. Nanomedicine, 3, 133 (2008)

[2] Oh KT, Lee ES, Kim DI, Bae YH, Int. J. Pharm., 358, 177 (2008)

[3] Zhao S, Lee JH, Macromol. Res., 17(3), 156 (2009)

[4] Shin YM, Lim KS, Jin JY, Jeong SI, Lee YM, Shin H, Kim KS, Macromol. Res., 17(12), 1039 (2009)

[5] Nobs L, Buchegger F, Gurny R, Allemann E, J. Pharm. Sci., 93, 1980 (2004)

[6] Jaracz S, Kuznetsova LV, Ojima I, Bioorg. Med. Chem., 13, 5043 (2005)

[7] Wong JY, Kuhl TL, Israelachvili JN, Mullah N, Zalipsky S, Science, 275(5301), 820 (1997)

[8] Bae MS, Lee KY, Park YJ, Mooney DJ, Macromol. Res., 15(5), 469 (2007)

[9] Kong G, Braun RD, Dewhirst MW, Cancer Res., 60, 4440 (2000)

[10] Lee ES, Gao Z, Bae YH, J. Control. Release, 132, 164 (2008)

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

[12] Lee ES, Kim D, Youn YS, Oh KT, Bae YH, Angew. Chem.-Int. Edit., 47, 2418 (2008)

[13] Lee ES, Gao Z, Kim D, Park K, Kwon IC, Bae YH, J. Control. Release, 129, 228 (2008)

[14] Khdair A, Handa H, Mao G, Panyam J, Eur. J. Pharm. Biopharm., 71, 214 (2009)

[15] Wu W, Air GM, Virology, 325, 340 (2004)

[16] Lagana A, Marino A, Fago G, Martinez BP, Anal. Chim. Acta, 306, 65 (1995)

[17] Yamauchi H, Yano T, Kato T, Tanaka I, Nakabayashi S, Higashi K, Miyoshi S, Yamada H, Int. J. Pharm., 113, 141 (1995)

[18] Gregoriadis G, Fernandes A, Mital M, McCormack B, Cell. Mol. Life Sci., 57, 1964 (2000)

[19] Wandinger KR, Hagenah JM, Kluter H, Rothermundt M, Peters M, Vieregge P, J. Neuroimmunol., 98, 214 (1999)

[20] Choi WY, Kim SJ, Lee NJ, Kwon MH, Yang IS, Kim MJ, Cheong SG, Kwon DH, Lee JY, Oh HB, Kang C, Antiviral Res., 84, 199 (2009)

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

[22] Ranjit V, Munasinghe N, Corrie JET, Kelly G, Martin SR, Biconjugate Chem., 18, 231 (2007)

[23] Darwish IA, Khedr AS, Askal HF, Mahmoud RM, J. Appl. Spectrosc., 73, 792 (2006)

[24] Lee SH, Baek HH, Kim JH, Choi SW, Macromol. Res., 17(12), 1010 (2009)

[25] Lee HJ, Kim SE, Kwon IK, Park C, Kim C, Yang J, Lee SC, Chem. Commun., 46, 377 (2010)

[26] Socha M, Bartecki P, Passirani C, Sapin A, Damge C, Lecompte T, Barre J, El Ghazouani F, Maincent P, J. Drug Target., 17, 575 (2009)

[27] Duek EAR, Zavaglia CAC, Belangero WD, Polymer, 40, 6456 (1999)