Antitumor Activities of Poly(Methacryloyl-D-Glucosamine)Prodrugs

Cho SH; Kim KS; Kang JK

Korea Polymer Journal, Vol.6, No.2, 188-192, June, 1998

Water-soluble polymer prodrugs such as poly(MANGE-co-MANG)(prodrug IV), poly (MANGF-co-MAA)(prodrug V), poly(MANGF-co-AAm)(prodrug VI), and poly(MAOGF-co-MAA)(prodrug VII) were synthesized. The amount of monomer prodrugs bound to polymer prodrugs were 4,5. 2.1, 1.17, and 30.1 mol%. The antitumor activity was tested against Sarcoma-180 ascites in female mice in vivo by intraperitoneal injection of the polymer prodrugs. Polymer prodrugs as poly(MANGF-co-MAA) and poly(MAOGF-co-MAA) showed relatively excellent antitumor effect despite the high dose of 100∼400 mg/kg but antitumor activity of poly(MANGF-co-AAm) prodrug was weaker than other polymer prodrugs. This results show that polymer prodrugs having positive charges show a rapid accumulation in the liver and subsequent rapid disappearance from plasma, and do not accumulate in the tumor to a great extent. But polymer prodrugs having negative charges show sustained plasma levels and a satisfactory uptake by the tumor. wae conclude that polymer prodrugs and monomer prodrugs showed relatively high biocompatibility and good antitumor activity by increasing the durability of drug activity and reducing the otxicity of 5-FU.

[References]

Downrange LG, Vogl O, Polymeric Drugs, Academic Press, New York (1978)
Ringsdorf H, J. Polym. Sci. Polym. Symp., 51, 135 (1975)
Kawakuchi T, J. Pharm. Sci., 81, 6 (1992)
Duncan R, J. Control. Release, 19, 331 (1992)
Gebelin CG, Baig W, Morgan RM, Clovwacky R, Polym. Prepr., 20, 600 (1979)
Ouchi T, Yuyama H, Vogl O, Makromol. Chem. Rapid Commun., 6, 815 (1985)
Ouchi T, Hagita K, Kawashima M, Inoi T, J. Bioact. Compat. Polym., 3, 53 (1988)
Zhuo RX, Liao J, Fan CL, Chem. J. Chin. Univ., 6(3), 244 (1990)
Young FS, Zhuo RX, Polym. J., 22, 592 (1990)
Ozaki S, Ike Y, Mizuno H, Ishikawa K, Hori M, Bull. Chem. Soc. Jpn., 50, 2406 (1977)
Ozaki S, Watanabe Y, Hoshiko T, Mizuno H, Ishikawa K, Hori M, Chem. Pharm. Bull., 32, 733 (1984)
Ozaki S, Watanabe Y, Ogasawara T, Yamauchi Y, Fujiwara K, Hoshi A, Iigo M, Chem. Pharm. Bull., 33, 2832 (1985)
Ozaki S, Watanabe Y, Hoshiko T, Nagase T, Ogasawara T, Fukukawa H, Uemura A, Ishikawa K, Mori M, Iigo M, Tokuzen R, Chem. Pharm. Bull., 34, 150 (1986)
Ouchi T, Fujie H, Jokei S, Sakamoto Y, Chikashita H, Inoi T, Vogl O, J. Polym. Sci. A: Polym. Chem., 24, 2059 (1986)
Ouchi T, Yuyama H, Vogl O, J. Polym. Sci. C: Polym. Lett., 25, 279 (1987)
Ouchi T, Yuyama H, Vogl O, J. Macromol. Sci.-Chem., A24, 1011 (1987)
Ouchi T, Hagita K, Kawashima M, Inoi T, Tashiro T, J. Control. Release, 8, 141 (1988)
Ouchi T, Banba T, Masuda H, J. Macromol. Sci.-Chem., A28(10), 959 (1991)
Ozaki S, Polym. J., 21, 955 (1989)
Yang T, Zhno R, Polym. J., 22, 572 (1990)
Akashi M, Miyauchi N, Morita N, Minota T, J. Bioactive Compatible Polym., 2, 232 (1987)
Akashi M, Iwasaki H, Miyauchi N, Sato T, Sunamoto J, Takemoto K, J. Bkoactive Compatible Polym., 4, 126 (1989)
Akashi M, Morita N, Miyachi O, Yasima E, Miyauchi N, Minota T, New Polym. Mater., 3, 31 (1991)
Sirca AE, Woodman RJ, J. Natl. Cancer Inst., 47, 377 (1971)
Susuki K, Tokoro A, Okawa Y, Susuki S, Macrobiol. Immunol. Chem., 30, 777 (1986)
Kim KS, Lim DS, Cho SH, Korea Polym. J., 4(1), 16 (1996)
Hattori H, Takada M, Fukushima M, Sasaki T, Matsuda A, J. Med. Chem., 39, 5005 (1996)
Takakura Y, Takagi A, Hashida M, Sezak H, Pharm. Res., 4, 293 (1987)

[Referenced By]

[1] Downrange LG, Vogl O, Polymeric Drugs, Academic Press, New York (1978)

[2] Ringsdorf H, J. Polym. Sci. Polym. Symp., 51, 135 (1975)

[3] Kawakuchi T, J. Pharm. Sci., 81, 6 (1992)

[4] Duncan R, J. Control. Release, 19, 331 (1992)

[5] Gebelin CG, Baig W, Morgan RM, Clovwacky R, Polym. Prepr., 20, 600 (1979)

[6] Ouchi T, Yuyama H, Vogl O, Makromol. Chem. Rapid Commun., 6, 815 (1985)

[7] Ouchi T, Hagita K, Kawashima M, Inoi T, J. Bioact. Compat. Polym., 3, 53 (1988)

[8] Zhuo RX, Liao J, Fan CL, Chem. J. Chin. Univ., 6(3), 244 (1990)

[9] Young FS, Zhuo RX, Polym. J., 22, 592 (1990)

[10] Ozaki S, Ike Y, Mizuno H, Ishikawa K, Hori M, Bull. Chem. Soc. Jpn., 50, 2406 (1977)

[11] Ozaki S, Watanabe Y, Hoshiko T, Mizuno H, Ishikawa K, Hori M, Chem. Pharm. Bull., 32, 733 (1984)

[12] Ozaki S, Watanabe Y, Ogasawara T, Yamauchi Y, Fujiwara K, Hoshi A, Iigo M, Chem. Pharm. Bull., 33, 2832 (1985)

[13] Ozaki S, Watanabe Y, Hoshiko T, Nagase T, Ogasawara T, Fukukawa H, Uemura A, Ishikawa K, Mori M, Iigo M, Tokuzen R, Chem. Pharm. Bull., 34, 150 (1986)

[14] Ouchi T, Fujie H, Jokei S, Sakamoto Y, Chikashita H, Inoi T, Vogl O, J. Polym. Sci. A: Polym. Chem., 24, 2059 (1986)

[15] Ouchi T, Yuyama H, Vogl O, J. Polym. Sci. C: Polym. Lett., 25, 279 (1987)

[16] Ouchi T, Yuyama H, Vogl O, J. Macromol. Sci.-Chem., A24, 1011 (1987)

[17] Ouchi T, Hagita K, Kawashima M, Inoi T, Tashiro T, J. Control. Release, 8, 141 (1988)

[18] Ouchi T, Banba T, Masuda H, J. Macromol. Sci.-Chem., A28(10), 959 (1991)

[19] Ozaki S, Polym. J., 21, 955 (1989)

[20] Yang T, Zhno R, Polym. J., 22, 572 (1990)

[21] Akashi M, Miyauchi N, Morita N, Minota T, J. Bioactive Compatible Polym., 2, 232 (1987)

[22] Akashi M, Iwasaki H, Miyauchi N, Sato T, Sunamoto J, Takemoto K, J. Bkoactive Compatible Polym., 4, 126 (1989)

[23] Akashi M, Morita N, Miyachi O, Yasima E, Miyauchi N, Minota T, New Polym. Mater., 3, 31 (1991)

[24] Sirca AE, Woodman RJ, J. Natl. Cancer Inst., 47, 377 (1971)

[25] Susuki K, Tokoro A, Okawa Y, Susuki S, Macrobiol. Immunol. Chem., 30, 777 (1986)

[26] Kim KS, Lim DS, Cho SH, Korea Polym. J., 4(1), 16 (1996)

[27] Hattori H, Takada M, Fukushima M, Sasaki T, Matsuda A, J. Med. Chem., 39, 5005 (1996)

[28] Takakura Y, Takagi A, Hashida M, Sezak H, Pharm. Res., 4, 293 (1987)