Abstract
The antitumor platinum moiety, (dach)Pt2+ (dach = trans(±)-1,2-diaminocyclohexane), was introduced to a poly(organophosphazene) using dicarboxylate spacers, glutamate or aspartate. After characterization of the polymeric conjugates by means of multinuclear (1H, 31P) NMR spectroscopy, elemental analysis, and gel-permeation chromatography (GPC), their in vitro hydrolytic behavior was examined in buffer solutions at different pHs and temperatures by monitoring with GPC. Hydrolytic properties of the conjugates were dependent on pH and temperature of the polymer solutions, and their degradation occurred more rapidly at lower pH and higher temperature. The antitumor activity of the conjugates was evaluated both in vitro and in vivo against the murine leukemia L1210 cell line and found to be dependent on the structures of the conjugates, and some of them exhibited higher in vivo activity than cisplatin and carboplatin.
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M. P. Hacker, E. B. Double and I. H. Krakoff, “Platinum Coordination Complexes in Cancer Chemotherapy,” Martinus Nijhoff Publishing, Boston, MA, 1984, pp 359—376.
A. W. Prestayko, S. T. Crooke and S. K. Carter, “Cisplatin Current Status and New Developments,” Academic Press, New York, N.Y., 1980, pp 317—321.
P. J. Loehrer and L. H. Einhorn, Drugs five years later. ciplatin, Ann. Intern. Med., 100, 704 (1984).
I. H. Krakoff, Cancer Treat Rep., 63, 1523 (1979).
K. J. Himmelstein, T. F. Patton, R. J. Belt, S. Taylor, A. J. Repta, and L. A. Sterson, Clin. Pharmacol. Ther., 29, 658 (1981).
R. F. Ozols and R. C. Young, Semin. Oncol., 11, 251 (1984).
W.-S. Hong, N. Saijo, Y, Sasaki, K. Minato, H. Nakano, K. Nakagawa, Y. Fujiwara, K. Nomura, and P.R. Twentyman, Int. J. Cancer, 41, 462 (1988).
J. H. Lee, J. Kopecek, and J. D. Andrade, J. Biomed. Mater. Res., 23, 351 (1989).
C. Delgado, G. E. Francis, and D. Fisher, Crit. Rev. Ther. Drug Carrier Sys., 9, 249 (1992).
B. Jeong, Y. H. Bae, D. S. Lee, and S. W. Kim, Nature, 388, 860 (1997).
H. Maeda, L. W. Seymour, and Y. Miyamoto, Bioconjugate Chem., 3, 351 (1992).
Y. Ohya, T. Masunaga, T. Baba, and T. Ouchi, J. Biomater. Sci., Polym. Ed., 7, 1085 (1996).
Y. Ohya, T. Masunaga, T. Baba, and T. Ouchi, Pure Appl. Chem., A33, 1005 (1996).
Y. Ohya, T. Masunaga, T. Ouchi, K. Ichinose, M. Nakashima, M. Ichikawa, and T. Kanematsu, Am. Chem. Soc., Symp. Ser., 709, 266 (1998).
B. Schechter, A. Neumann, M. Wilchek, and R. Arnon, J. Control. Rel., 10, 75 (1989).
M. Yokoyama, T. Okano, Y. Sakurai, S. Suwa, and K. Kataoka, J. Control. Rel., 39, 351 (1996).
S.-C. Song, S. B. Lee, J.-I. Jin, and Y. S. Sohn, Macromolecules, 32, 2188 (1999).
S. B. Lee, S.-C. Song, J.-I. Jin, and Y. S. Sohn, Macromolecules, submitted.
S.-C. Song, S. B. Lee, J.-I. Jin, and Y. S. Sohn, Macromolecules, submitted.
Y. S. Sohn, H.-G. Baek, Y. H. Cho, Y.-A. Lee, O.-S. Jung, C. O. Lee, and Y. S. Kim, Int. J. Pharmaceutics, 153, 79 (1997).
S.-C. Song and Y. S. Sohn, J. Control. Rel, 55, 161 (1998).
J. D. Greenstein and M. Winitz, “Chemistry of the Amino Acids,” John Wiley and Sons, New York, N.Y., 1961, pp 925—924.
R. C. Harrison, C. A. McAuliffe, and A. M. Zaki, Inorg. Chim. Acta, 46, 15 (1980).
Y. S. Sohn, Y. H. Cho, H.-G. Baek, and O.-S. Jung, Macromolecules, 28, 7566 (1995).
J. H. L. Crommen, E. H. Schacht, and E. H. G. Mense, Biomaterials, 13, 601 (1992).
H. R. Allcock, S. R. Pucher, and A. G. Scopelianos, Macromolecules, 27, 1071 (1994).
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Lee, S., Song, SC., Jin, JI. et al. Synthesis and Antitumor Activity of Polyphosphazene/Methoxy-Poly(ethylene glycol)/(Diamine)platinum(II) Conjugates. Polym J 31, 1247–1252 (1999). https://doi.org/10.1295/polymj.31.1247
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DOI: https://doi.org/10.1295/polymj.31.1247
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