Influence of Molecular Weight on the Biological Effects of Benzocaine Modified Maleic Anhydride Copolymer

Abstract

A new series of polyanionic polymers with antitumor activity were synthesized by conjugating ethyl 4-aminobenzoate onto a series of maleic anhydride (MA) copolymers of vinyl acetate, methyl methacrylate, and styrene. The molecular weight of these copolymers ranged from 18 10³ to 2 10⁵. The in vivo and in vitro biological tests showed that the maleic anhydride synthesized copolymers exhibit prolonged half-life in serum, accumulate in K₅₆₂ erythroleukemia solid tumors, and inhibit tumor growth. The antitumor activity appears to be increased by the enhanced permeability and retention (EPR) effect which is related to the macromolecular size of the antitumor agent.

Keywords

MA copolymers anticancer activity polyanionic polymers conjugated polymers EPR effect

Get full access to this article

View all access options for this article.

References

Alberts, B. (1989). Molecular Biology of the Cell, 2nd edn, pp. 323-340, Garland, New York .

Panaitescu, L. and Ottenbrite, R. M. (2002). J. Bioact. Compat. Polym., 17: 357-374 .

Butler, G. B. (1980). In: Anionic Polymer Drugs, Donaruma, L. G. , Ottenbrite, R. M. , and Vogi, O. (eds), p. 49-49, John Wiley, New York .

Ottenbrite, R. M. , Regelson, W. , Kaplan, A. , Carchman, R. , Morahan, P. , and Munson, A. (1978). In: Polymer Drugs, Donaruma, L. G. and Vogi, O. (eds), John Wiley, New York .

Uglea, C. V. , Va'ta'janu, A. , Offenberg, H. , Grecianu, A. , Ottenbrite R. M. , and Negulescu, I. I. (1993). Polymer, 34: 3298-3301 .

Uglea, C. V. , Panaitescu, L. , Spiridon, D. , Ursu, D. , Popa, I. , and Ottenbrite, R. M. (1996). J. Biomater. Sci., Polymer Edn, 8: 269-280 .

Popa, I. , Offenberg, H. , Beldie, C. , and Uglea, C. V. (1997). Eur. Polym. J., 33: 1511-1514 .

Becton Dickinson (1992). Catalogue of Cell Lines and Hybridomes, 7th edn, p. 129-129, Becton Dickinson .

Freshing, R. I. (1984). Practical Approach Series, Richwood, D. and Hames, B. D. (eds), Oxford, Washington, DC .

10.

Pollak, V. A. and Fidler, I. J. (1982). J. Nate. Cancer Inst., 69: 137-144 .

11.

Markavericj, B. M. , Gregory, R. R. , Alejandro, M. A. , Johnson, G. A. , and Middleditch, B. S. (1988). J. High. Resolut. Chromatogr., Chromatogr. Commun., 11: 605-607 .

12.

Brown, R. R. , Bain, R. , and Jordan, U. C. (1983). J. Chromatogr., 272: 351-362 .

13.

Uglea, C. V. and Ottenbrite, R. M. (1996). Polysaccharides in Medicinal Applications, Dumitriu, S. (ed.), Ch. 26, Marcel Dekker Inc., New York .

14.

Ringsdorf, H. , Schlarb, B. , and Ventmer, J. (1988). Angew. Chem. Int. Ed. Engl., 27: 113-139 .

15.

Matsumura, Y. and Maeda, H. (1986). Cancer Res., 46: 6387-6391 .

16.

Maeda, H. , Saymour, L. , and Miyamoto, Y. (1992). Bioconjugate Chem., 3: 351-359 .

17.

Maeda, H. (1992). J. Controlled Rel., 19: 315-321 .