This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Popa, M. Articles by Uglea, C. V. Search for Related Content Social Bookmarking                         What's this?

Antitumoral Activity Induced by Alkylating Agents Conjugated to Poly(maleic anhydride-alt-vinyl acetate)

Department of Natural and Synthetic Polymers, "Gh.Asachi" Technical University of Iai, Bd. D. Mangeron, No 71 A, 700050 Iai, Romania, marpopa{at}ch.tuiasi.ro

Valeriu Sunel

Department of Organic Chemistry, "Al.I.Cuza" University of Iai, Bd. Carol No 11, 700506, Iai, Romania

Nicoleta Dulea

Department of Organic Chemistry, "Al.I.Cuza" University of Iai, Bd. Carol No 11, 700506, Iai, Romania

Aura Angelica Popa

"Petre Andrei" University, Str. Ghica Voda, No. 13, 700400, Iasi, Romania

Raphael M. Ottenbrite

Virginia Commonwealth University, Richmond, USA

Constantin V. Uglea

Department of Biomedical Engineering, University of Medicine and Pharmacy, Str. Universitatii 16, 700015 Iasi, Romania

New polyanionic polymer conjugates with antitumoral activity are synthesized by chemically binding mustard type alkylating derivatives of di-(ß-chloroethyl)-amine and tri-(ß-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.

Key Words: poly(maleic anhydride-alt-vinyl acetate) • tri-(ß-chloroethyl)-amine • di-(ß-chloroethyl)-amine • antitumoral activity • bioactive polymers • carcinosarcoma Walker 256 • tumors.

References

• unel, V. and oldea, C. (1995). Indian J. Chem., 34(B): 227—229.
• unel, V., Popa, M., Popa, A. and oldea, C. (2000). Cellulose Chemistry and Technology, 34: 269—274.
• Xie, G., Gupta, R. and Lown, J.W. (1995). Anti Cancer Drug Design, 10(1): 389—409.
• Gupta, R., Wang, H., Huang, L. and Lown, J.W. (1995). Anti Cancer Drug Design, 10(1): 25—41.
• unel, V. and oldea, C. (1993). Comp. Rend. Acad. Bulg. Sci., 46: 61—63.[CrossRef]
• Sunel, V., Cecal, A., Soldea, C. and Asandei, N. (1995). Rev. Roumaine de chimie, 40: 763—768.
• Janson, P.E., Kenne, L. and Linberg, B. (1975). Carbohydr. Res., 45: 275—282.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Popa, M., unel, V. and Blit-Rusu, L. (2003). Journal of Biomaterials Applications, 18: 83—94.[Abstract/Free Full Text]
• Dumitriu, S. and Popa, M. (1988). Makromolekulare Chemie, 189: 103—110.[CrossRef]
• Butler, G.B. (1980). In: Donaruma, L.G., Ottenbrite, R.M. and Vogi, O. (eds), Anionic Polymer Drugs, p. 39, John Wiley, New York.
• 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.
• Uglea, C.V., Vatajanu, A., Offenberg, H., Grecianu, A., Ottenbrite, R.M. and Negulescu, I.I. (1993). Polymer, 34: 3298—3301.[CrossRef][Web of Science]
• 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.
• Patel, H., Raval, D.A., Madamwar, D. and Patel, S.R. (1997). Angew. Makromol. Chem., 245: 1—8.[CrossRef]
• Patel, H., Raval, D.A., Madamwar, D. and Patel, S.P. (1998). Angew. Makromol. Chem., 263: 25—30.[CrossRef]
• Lee, Y.S. and Byoun, Y.S. (2002). Bull. Korean Chem. Soc., 23: 1833—1835; (2001). J. Ind. Eng. Chem., 7: 310—317.
• Jeong, J.H., Byoum, Y.S. and Lee, Y.S. (2002). Reactive and Functional Polymers, 50: 257—263.[CrossRef]
• Uglea, C., Parv, A., Dumitriu, A., Corjan, M. and Ottenbrite, R. (2006). J. Bioact. Compat. Polym., 21(5): 399—413.[Abstract/Free Full Text]
• Sunel, V., Popa, M., Dumitriu, C.L., Ciobanu, A., Bunia, I. and Popa, A.A. (2005). Reactive and Functional Polymers, 65(3): 367—380.[CrossRef]
• Bacu, E., Chitanu, G.C., Couture, A., Grandclaudon, P., Singurel, Gh. and Carpov, A. (2002). European Polymer Journal, 38: 1509—1513.[CrossRef][Web of Science]
• Pollak, V.A. and Fidler, I.J. (1982). J. Natl. Cancer Inst., 69: 137—141.[Web of Science][Medline] [Order article via Infotrieve]
• 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.
• Brown, R.R., Bain, R. and Jordan, V.C. (1983). J. Chromatogr., 272: 351—356.[Web of Science][Medline] [Order article via Infotrieve]
• Uglea, C.V., Panaitescu, L., Spiridon, D., Ursu, D., Popa, I. and Ottenbrite, R.M. (1996). J. Biomater. Sci. Polymer Edn., 8: 269—280.
• Panaitescu, L. and Ottenbrite, R.M. (2002). J. Bioact. Compat. Polymers, 17: 367—373.
• Ringsdorf, H., Schlarb, B. and VBentmer, J. (1988). Angew. Chem. Int. Ed. Engls., 27: 113—139.[CrossRef]
• Matsumura, Y. and Maeda, H. (1986). Cancer Res., 46: 6387—6391.[Abstract/Free Full Text]
• Maeda, H., Seymour, L. and Miyamoto, Y. (1992). Bioconjugate Chem., 3: 351—359.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Maeda, H. (1992). J. Controlled Rel., 19: 315—321.[CrossRef][Web of Science]
• Uglea, C.V., Pârv, A., Corjan, M., Dumitriu, A. and Ottenbrite, R.M. (2005). J. Bioact. Compat. Polymers, 20: 571—583.[CrossRef]
• Thatte, S., Datar, K. and Ottenbrite, R.M. (2005). J. Bioact. Compat. Polym., 20(6): 585—601.[Abstract]
• Chiellini, F. (2006). Journal of Bioactive and Compatible Polymers, 21: 257—271.[CrossRef]
• Jacob, L.S. (1992). Pharmacology, Chap 11. 3rd edn, National Medical Series, Williams and Wilkins, Baltimore.

Journal of Bioactive and Compatible Polymers, Vol. 22, No. 6, 651-666 (2007)
DOI: 10.1177/0883911507084424


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				S.-M. Lee, B.-G. Kim, C.-S. Ha, I. Chung, and Dong Xie Syntheses and Evaluations of Antitumor and Antiangiogenic Compounds Conjugated with 5-Fluorouracil and Ascorbic Acid Journal of Bioactive and Compatible Polymers, September 1, 2008; 23(5): 473 - 489. [Abstract] [PDF]

				C. Bayram, E. B. Denkbas, E. Kilicay, B. Hazer, H. B. Cakmak, and I. Noda Preparation and Characterization of Triamcinolone Acetonide-loaded Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHx) Microspheres Journal of Bioactive and Compatible Polymers, July 1, 2008; 23(4): 334 - 347. [Abstract] [PDF]

This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Popa, M. Articles by Uglea, C. V. Search for Related Content Social Bookmarking                         What's this?