Abstract
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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
W. H. D. Jong and P. Borm, Int. J. Nanomedicine, 3, 133 (2008).
K. T. Oh, E. S. Lee, D. I. Kim, and Y. H. Bae, Int. J. Pharm., 358, 177 (2008).
S. Zhao and J. Lee, Macromol. Res., 17, 156 (2009).
Y. M. Shin, K. S. Lim, J. Y. Jin, S. I. Jeong, Y. M. Lee, H. Shin, and K. S. Kim, Macromol. Res., 17, 1039 (2009).
L. Nobs, F. Buchegger, R. Gurny, and E. Allemann, J. Pharm. Sci., 93, 1980 (2004).
S. Jaracz, L. V. Kuznetsova, and I. Ojima, Bioorg. Med. Chem., 13, 5043 (2005).
J. Wong, T. L. Kuhl, J. N. Israelachvili, N. Mullah, and S. Zalipsky, Science, 275, 820 (1997).
M. S. Bae, K. Y. Lee, Y. J. Park, and D. J. Mooney, Macromol. Res., 15, 469 (2007).
G. Kong, R. D. Braun, and M. W. Dewhirst, Cancer Res., 60, 4440 (2000).
E. S. Lee, Z. Gao, and Y. H. Bae, J. Control. Release, 132, 164 (2008).
E. S. Lee, K. Na, and Y. H. Bae, Nano Lett., 5, 325 (2005).
E. S. Lee, D. Kim, Y. S. Youn, K. T. Oh, and Y. H. Bae, Angew. Chem. Int. Ed., 47, 2418 (2008).
E. S. Lee, Z. Gao, D. Kim, K. Park, I. C. Kwon, and Y. H. Bae, J. Control. Release, 129, 228 (2008).
A. Khdair, H. Handa, G. Mao, and J. Panyam, Eur. J. Pharm. Biopharm., 71, 214 (2009).
W. Wu and G. M. Air, Virology, 325, 340 (2004).
A. Lagana, A. Marino, G. Fago, and B. P. Martinez, Anal. Chim. Acta, 306, 65 (1995).
H. Yamauchi, T. Yano, T. Kato, I. Tanaka, S. Nakabayashi, K. Higashi, S. Miyoshi, and H. Yamada, Int. J. Pharm., 113, 141 (1995).
G. Gregoriadis, A. Fernandes, M. Mital, and B. McCormack, Cell. Mol. Life Sci., 57, 1964 (2000).
K. P. Wandinger, J. M. Hagenah, H. Kluter, M. Rothermundt, M. Peters, and P. Vieregge, J. Neuroimmunol., 98, 214 (1999).
W. Y. Choi, S. J. Kim, N. J. Lee, M. H. Kwon, I. S. Yang, M. J. Kim, S. G. Cheong, D. H. Kwon, J. Y. Lee, H. B. Oh, and C. Kang, Antiviral Res., 84, 199 (2009).
S. Zalipsky and G. Barany, J. Bioact. Compat. Polym., 5, 227 (1990).
V. Ranjit, N. Munasinghe, J. E. T. Corrie, G. Kelly, and S. R. Martin, Biconjugate Chem., 18, 231 (2007).
I. A. Darwish, A. S. Khedr, H. F. Askal, and R. M. Mahmoud, J. Appl. Spectrosc., 73, 792 (2006).
S. H. Lee, H. H. Baek, J. H. Kim, and S. W. Choi, Macromol. Res., 17, 1010 (2009).
H. J. Lee, S. E. Kim, I. K. Kwon, C. Park, C. Kim, J. Yang, and S. C. Lee, Chem. Commun., 46, 377 (2010).
M. Socha, P. Bartecki, C. Passirani, A. Sapin, C. Damgé, T. Lecompte, J. Barré, F. El Ghazouani, and P. Maincent, J. Drug Target., 17, 575 (2009).
E. A. R. Duek, C. A. C. Zavaglia, and W. D. Belangero, Polymer, 40, 6456 (1999).
Author information
Authors and Affiliations
Corresponding author
Additional information
These authors contributed equally to this work.
Rights and permissions
About this article
Cite this article
Ahn, Y.S., Baik, H.J., Lee, B.R. et al. Preparation of multifunctional polymeric micelles for antiviral treatment. Macromol. Res. 18, 747–752 (2010). https://doi.org/10.1007/s13233-010-0802-8
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13233-010-0802-8