Abstract
The purpose of this study is to ascertain the relationship between the structure of an amphiphilic nonionic polymer and its toxicity for cells (cytotoxicity) growing in a culture. To this end, 16 polymers of different architectures and chemical structures are tested, namely, linear triblock copolymers of poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) (Pluronics); diblock copolymers of propylene oxide, ethylene oxide, and hyperbranched polyglycerol; alternating and diblock copolymers of ethylene oxide and dimethylsiloxane; and two surfactants containing linear (Brij-35) or branched (Triton X-100) aliphatic chains. Polymer-cell interaction is assayed in a culture medium in the absence of serum. Effective concentrations of the polymers causing 50% cell death, EC50, vary within three orders of magnitude. Toxic concentrations of the alternating copolymer, Triton X-100, and Brij-35 are lower than their CMC values. In contrast, all block copolymers, regardless of their chemical structures, become toxic at concentrations above the CMC; that is, they acquire cytotoxicity only in the micellar form. The EC50 values of the copolymers depend on their hydrophilic-liphophilic balance (HLB) through the following empirical formula: EC50 × 106 = 8.71 × HLB2.1. This relationship makes it possible to predict the cytotoxic concentration region of a block copolymer of a known structure.
Similar content being viewed by others
References
L. G. Lunsted and I. Schmolka, in Block and Graft Copolymerization, Ed. by R. J. Ceresa (Wiley, London, 1976), Vol. 2, p. 174.
Medico-Biological Aspects of Application of Perfluorinated Hydrocarbon Emulsions, Ed. by G. R. Ivanitskii and F. F. Beloyartsev (Pushchino, 1983), p. 9.
R. M. Nalbandian, R. L. Henry, K. W. Balko, D. V. Adams, and N. R. Neuman, J. Biomed. Mater. Res. 21, 1135 (1987).
S. M. Moghimi and A. C. Hunter, Trends Biotechnol. 18, 412 (2000).
P. H. Elworthy and J. F. Ireon, in Nonionic Surfactants, Ed. by M. J. Shick (Marcel Dekker, New York, 1971), p. 9317.
F. Seeballuck, M. B. Ashford, and C. M. O’Driscoll, Pharm. Res. 20, 1085 (2003).
A. Warren, V. Benseler, V. C. Cogger, P. Bertolino, and D. G. Le Couteur, Toxicol. Pathol. 39, 390 (2011).
E. A. Coors, H. Seybold, H. F. Merk, and V. Mahler, Ann. Allergy Asthma Immunol. 95, 593 (2005).
H. Gelderblom, J. Verweij, K. Nooter, and A. Sparreboom, Eur. J. Cancer 37, 1590 (2001).
T. Demina, I. Grozdova, O. Krylova, A. Zhirnov, V. Istratov, H. Frey, H. Kautz, and N. Melik-Nubarov, Biochemistry 44, 4042 (2005).
D. N. Pavlov, T. Yu. Dorodnykh, O. V. Zaborova, and N. S. Melik-Nubarov, Polymer Science, Ser. A 51, 295 (2009) [Vysokomol. Soedin., Ser. A 51, 428 (2009)].
A. Chattopadhyay and E. London, Anal. Biochem. 139, 408 (1984).
E. V. Nam, A. E. Zhirnov, E. A. Litmanovich, N. S. Melik-Nubarov, and I. D. Grozdova, Polymer Science, Ser. A 52, 907 (2010) [Vysokomol. Soedin., Ser. A 52, 1578 (2010)].
T. Mosmann, J. Immunol. Methods 65, 55 (1983).
V. Yu. Alakhov, E. Yu. Moskaleva, E. V. Batrakova, and A. V. Kabanov, Bioconjug. Chem. 7, 209 (1996).
E. V. Batrakova, U. Shu, S. V. Vinogradov, V. Yu. Alakhov, D. W. Miller, and A. V. Kabanov, J. Pharm. Exp. Ther. 299, 483 (2001).
E. Batrakova, Shengmin Lee, Shu Li, An. Venne, V. Alakhov, and A. Kabanov, Pharm. Res. 16, 1373 (1999).
P. Alexandridis, J. F. Holzwarthf, and T. A. Hatton, Macromolecules 27, 2414 (1994).
I. Schmolka and A. J. Raymond, Am. Oil Chem. Soc. 42, 1088 (1965).
E. V. Batrakova, H. Huai-Yun, V. Yu. Alakhov, D. W. Miller, and A. V. Kabanov, Pharm. Res. 15, 850 (1998).
J. R. Lopes and W. Loh, Langmuir 14, 750 (1998).
A. V. Kabanov, I. R. Nazarova, I. V. Astafieva, E. V. Batrakova, V. Yu. Alakhov, A. V. Yaroslavov, and V. A. Kabanov, Macromolecules 28, 2303 (1995).
D. W. Miller, E. V. Batrakova, T. O. Waltner, V. Yu. Alakhov, and A. V. Kabanov, Bioconjug. Chem. 8, 649 (1997).
R. J. Holland, E. J. Parker, K. Guiney, and F. R. Zeld, J. Phys. Chem. 99, 11981 (1995).
V. I. Slepnev, L. E. Kuznetsova, A. N. Gubin, E. V. Batrakova, V. Yu. Alakhov, and A. V. Kabanov, Biochem. Int. 26, 587 (1992).
G. Wanka, H. Hoffmann, and W. Ulbricht, Macromolecules 27, 4145 (1994).
G. Wanka, H. Hoffmann, and W. Ulbricht, Colloid Polym. Sci. 268, 101 (1990).
Y. Zhang and Y. M. Lam, J. Colloid Interface Sci. 306, 398 (2007).
P. Linse and M. Malmsten, Macromolecules 25, 5434 (1992).
P. Alexandridis, V. Athanassiou, S. Fukuda, and T. A. Hatton, Langmuir 10, 2604 (1994).
E. Hecht and H. Hoffmann, Langmuir 10, 86 (1994).
S. R. Croy and G. S. Kwon, J. Controlled Release 95, 161 (2004).
M. Y. Kozlov, N. S. Melik-Nubarov, E. V. Batrakova, and A. V. Kabanov, Macromolecules 33, 3305 (2000).
A. E. Zhirnov, D. N. Pavlov, T. V. Demina, G. A. Badun, I. D. Grozdova, and N. S. Melik-Nubarov, Polymer Science, Ser. A 48, 1202 (2006) [Vysokomol. Soedin., Ser. A 48, 2023 (2006)].
H. I. Park, S. Lee, A. Ullah, Q. Cao, and Q. X. Sang, Anal. Biochem. 396, 262 (2010).
X. Wen, PhD Thesis (Univ. of Saskatchewan, Saskatoon, 1999).
K. Glenn, A. Van Bommel, S. Bhattacharya, and R. Palepu, Colloid Polym. Sci. 283, 845 (2005).
P. Linse, Macromolecules 27, 6404 (1994).
M. G. Chernysheva, Z. A. Tyasto, and G. A. Badun, Zh. Fiz. Khim. 83, 356 (2009).
H. Heerklotz and J. Seelig, Biophys. J. 78, 2435 (2000).
R. Lipowsky, Europhys. Lett. 30, 197 (1995).
A. De la Maza and J. L. Parra, Biochem. J. 3, Part 3, 907 (1994).
O. López, A. De la Maza, L. Coderch, C. López-Iglesias, E. Wehrli, and J. L. Parra, FEBS Lett. 426, 314 (1998).
P. Harmon, D. Cabral-Lilly, R. A. Reed, F. P. Maurio, J. C. Franklin, and A. Janoff, Anal. Biochem. 250, 139 (1997).
Author information
Authors and Affiliations
Corresponding author
Additional information
Original Russian Text © O.A. Budkina, T.V. Demina, T.Yu. Dorodnykh, N.S. Melik-Nubarov, I.D. Grozdova, 2012, published in Vysokomolekulyarnye Soedineniya, Ser. A, 2012, Vol. 54, No. 9, pp. 1385–1395.
This work was supported by the Russian Foundation for Basic Research, project no. 09-03-00445.
Rights and permissions
About this article
Cite this article
Budkina, O.A., Demina, T.V., Dorodnykh, T.Y. et al. Cytotoxicity of nonionic amphiphilic copolymers. Polym. Sci. Ser. A 54, 707–717 (2012). https://doi.org/10.1134/S0965545X12080020
Published:
Issue Date:
DOI: https://doi.org/10.1134/S0965545X12080020