New polyanionic polymer conjugates with antitumoral activity are synthesized by chemically binding mustard type alkylating derivatives of di-(β-chloroethyl)-amine and tri-(β-chloroethyl)-amine, respectively, onto poly(maleic anhydride-alt-vinyl acetate). The structures of the compounds are verified by FTIR, 1H NMR, and elemental analysis. The antitumoral activity of these polymeric drugs is evaluated in vivo using carcinosarcoma Walker 256 solid tumors in Wister rats. The conjugates exhibit antitumor regression (ATR) values between 25 and 44% depending on comonomers' structure. In addition, an accumulation in the solid tumors (enhanced permeability and retention (EPR) effect) by these compounds is observed. These compounds also cause small organotropic effects, such as increases in the liver, spleen, and kidney weight.
Şşunel, V. and Şşoldea , C. (1995). Indian J. Chem., 34(B): 227—229.
2.
Şşunel, V., Popa, M., Popa, A. and Şşoldea, C. (2000). Cellulose Chemistry and Technology, 34: 269—274.
3.
Xie, G., Gupta, R. and Lown, J.W. (1995). Anti Cancer Drug Design, 10(1): 389—409.
4.
Gupta, R., Wang, H., Huang, L. and Lown, J.W. (1995). Anti Cancer Drug Design, 10(1): 25—41.
5.
Şşunel, V. and Şşoldea , C. (1993). Comp. Rend. Acad. Bulg. Sci., 46: 61—63.
6.
Sunel, V., Cecal, A., Soldea, C. and Asandei, N. (1995). Rev. Roumaine de chimie, 40: 763—768.
7.
Janson, P.E. , Kenne, L. and Linberg, B. (1975). Carbohydr. Res., 45: 275—282.
8.
Popa, M., Şşunel, V. and Bălăită-Rusu, L. (2003). Journal of Biomaterials Applications, 18: 83—94.
9.
Dumitriu, S. and Popa, M. (1988). Makromolekulare Chemie , 189: 103—110.
10.
Butler, G.B. (1980). In: Donaruma, L.G., Ottenbrite, R.M. and Vogi, O. (eds), Anionic Polymer Drugs , p. 39, John Wiley, New York.
11.
Ottenbrite, R.M. , Regelson, W., Kaplan , A., Carchman, R., Morahan, P. and Munson, A. (1978). In: Donaruma, L.G., Ottenbrite, R.M. and Vogi, O. (eds), Polymer Drugs, John Wiley, New York.
12.
Uglea, C.V. , Vatajanu, A., Offenberg , H., Grecianu, A., Ottenbrite, R.M. and Negulescu , I.I. (1993). Polymer, 34: 3298—3301.
13.
Culbertson, B.M. (1987). Maleic and Fumaric Polymers, In: Encycl. Polym. Sci. Eng., 2nd edn, Vol 14, pp. 225—294, John Wiley and Sons, New York.
14.
Patel, H., Raval, D.A., Madamwar, D. and Patel, S.R. (1997). Angew. Makromol. Chem., 245: 1—8.
15.
Patel, H., Raval, D.A., Madamwar, D. and Patel, S.P. (1998). Angew. Makromol. Chem., 263: 25—30.
16.
Lee, Y.S. and Byoun, Y.S. (2002). Bull. Korean Chem. Soc., 23: 1833—1835; (2001). J. Ind. Eng. Chem., 7: 310—317.
17.
Jeong, J.H., Byoum, Y.S. and Lee, Y.S. (2002). Reactive and Functional Polymers, 50: 257—263.
18.
Uglea, C., Parv, A., Dumitriu, A., Corjan, M. and Ottenbrite, R. (2006). J. Bioact. Compat. Polym., 21(5): 399—413.
19.
Sunel, V., Popa, M., Dumitriu, C.L., Ciobanu, A., Bunia, I. and Popa, A.A. (2005). Reactive and Functional Polymers, 65(3): 367—380.
20.
Bacu, E., Chitanu, G.C., Couture, A., Grandclaudon, P., Singurel, Gh. and Carpov, A. (2002). European Polymer Journal, 38: 1509—1513.
21.
Pollak, V.A. and Fidler, I.J. (1982). J. Natl. Cancer Inst. , 69: 137—141.
22.
Markaverich, B.M., Gregory, R.R., Alejandrov , M.A., Johnson, G.A. and Middledich , B.S. (1998). J. High Resolut. Chromatoyc., Chromatogr. Commun., 11: 605—607.
23.
Brown, R.R. , Bain, R. and Jordan, V.C. (1983). J. Chromatogr., 272: 351—356.
24.
Uglea, C.V. , Panaitescu, L., Spiridon , D., Ursu, D., Popa, I. and Ottenbrite, R.M. (1996). J. Biomater. Sci. Polymer Edn., 8: 269—280.
25.
Panaitescu, L. and Ottenbrite, R.M. (2002). J. Bioact. Compat. Polymers, 17: 367—373.
26.
Ringsdorf, H., Schlarb, B. and VBentmer, J. (1988). Angew. Chem. Int. Ed. Engls., 27: 113—139.
27.
Matsumura, Y. and Maeda, H. (1986). Cancer Res. , 46: 6387—6391.
28.
Maeda, H., Seymour, L. and Miyamoto, Y. (1992). Bioconjugate Chem., 3: 351—359.
29.
Maeda, H. (1992). J. Controlled Rel., 19: 315—321.
30.
Uglea, C.V. , Pârv, A., Corjan , M., Dumitriu, A. and Ottenbrite, R.M. (2005). J. Bioact. Compat. Polymers, 20: 571—583.
31.
Thatte, S., Datar, K. and Ottenbrite, R.M. (2005). J. Bioact. Compat. Polym. , 20(6): 585—601.
32.
Chiellini, F. (2006). Journal ofBioactive and Compatible Polymers, 21: 257—271.
33.
Jacob, L.S. (1992). Pharmacology, Chap 11. 3rd edn, National Medical Series, Williams and Wilkins, Baltimore.
