Anticancer Activity of Polyunsaturated Fatty Acid Emulsion Stabilized by Hydrophobized Polysaccharide

Abstract

An oil-in-water emulsion of selectively cytotoxic α-linolenic acid (ALA, C18:3ω3) was stabilized with cholesterol-bearing pullulan (CHP-55-2.1), and the in vivo anticancer effect of the O/W-emulsion was investigated. The O/W-emulsion was prepared by ultrasonication of a mixture of CHP and ALA in the presence or absence of trioctanoylglyceride (TriC₈). The colloidal stabil ity of the CHP/ALA-emulsion was largely improved by adding TriC₈. Intraperi toneal injection of the CHP/ALA-emulsion effectively prolonged the survival time of C3H/He mice which received an intraperitoneal transplantation of MM46 mammary tumor cells. The growth of these tumor cells subcutaneously transplanted in C3H/He mice was also significantly suppressed without any loss of body weight when CHP/ALA/TriC₈-emulsion was intravenously injected. By using this colloidally stable O/W emulsion, it is possible to systemically ad minister a lipophilic liquid drug.

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References

Golo, M.G. , B. Bloj and R.N. Farias. 1975. J. Biol. Chem., 250:6204.

Kaduce, T.L. , A.B. Awad , L.J. Fontenelle and A.A. Spector. 1977. J. Biol. Chem., 252:6624.

Mahoney, E.M. , W.A. Scott , F.R. Landsberger , A.L. Hamill and Z.A. Cohn. 1980. J. Biol. Chem., 255:4910.

Begin, M.E. , U.N. Das , G. Ells and D.F. Horrobin. 1985. Prostagl. Leukotr. Med., 19:177.

Giaro, L.A. , A.C. Ruck , R.C. Cantrill and B.C. Davidson. 1986. Anticancer Research, 6:241.

Begin, M.E. , U.N. Das and G. Ells. 1986. Prog. Lipid Res., 25:573.

Begin, M.E. , G. Ells , U.N. Das and D.F. Horrobin. 1986. J. Natl. Cancer Inst., 77:1053.

Fukui, H. , T. Sato and J. Sunamoto. Biochim. Biophys. Acta., submitted.

Numata, M. and Y. Isoda. 1986. Chemistry and Chemical Industry, 39:151.

10.

Sunamoto, J. , T. Sato, T. Taguchi and H. Hamazaki. 1992 Macromolecules, 25:5665.

11.

Sunamoto, J. and T. Sato. 1989. J. Chem. Soc. Jpn., p. 161.

12.

Akiyoshi, K. , H. Takanabe , T. Sato , T. Sato , H. Kondo and J. Sunamoto. 1990. Chem. Lett., p. 473.

13.

Sunamoto, J. , T. Sato , M. Hirota , K. Fukushima , K. Hiratani and K. Hara. 1987. Biochim. Biophys. Acta ., 898:323.

14.

Sato, T. , J. Sunamoto , N. Ishii and T. Koji. 1988. J. Bioactive and Compatible Polym. , 3:195.

15.

Akiyoshi, K. , S. Deguchi, N. Moriguchi, S. Yamaguchi and J. Sunamoto. 1993 Macromolecules, 26:3062.

16.

Akiyoshi, K. , S. Yamaguchi and J. Sunamoto. 1991. Chem. Lett., p. 1263.

17.

Akiyoshi, K. , K. Nagai , T. Nishikawa and J. Sunamoto. 1992. Chem. Lett., p. 1727.

18.

Carlsson, A. , T. Sato and J. Sunamoto. 1989. Bull. Chem. Soc. Jpn., 62:791.

19.

Iwamoto, K. , T. Kato , M. Kawahara , N. Koyama , S. Watanabe , Y. Miyake and J. Sunamoto. 1991. J. Pharm. Sci., 80:219.

20.

Yamaguchi, S. , H. Fukui , K. Akiyoshi , T. Sato and J. Sunamoto. 1992. J. Chem. Soc. Jpn. , p. 186.

21.

Begin, M.E. , G. Ells and D.F. Horrobin. 1988. J. Natl. Cancer Inst., 80:188.

22.

Reddy, B.S. and H. Maruyama. 1986. Cancer Res., 46:3367.

23.

Braden, L.M. and K.K. Carroll. 1986. Lipids, 21:285.

24.

Jurkowski, J.J. and W.T. Cave , Jr. 1985. J. Natl. Cancer Inst., 74:1145.

25.

Hirose, M. , A. Masuda , T. Kato , N. Ito , K. Kamano and H. Okuyama. 1988. The 48th Annual Meeting on Proceedings of the Japanese Cancer Association, p. 72.

26.

Narisawa, H. , M. Takahashi , N. Kusaka , Y. Yamazaki , H. Koyama , H. Kotanagi , Y. Nishizawa , M. Kotsugai , Y. Isoda and J. Hirano. 1990. J. Clin. Exp. Med. (IGAKU NO AYUMI), 153:103.

27.

. Fritsche, K.L. 1988. J. Am. Oil Chem. Soc , 65:509.

28.

Karmali, R.A. , J. Marsh and C. Fuchs. 1984. J. Natl. Cancer Inst. , 73:457.

29.

Zhu, Y.P. , Z.W. Su and C.H. Li. 1989. J. Natl. Cancer Inst., 81:1302.

30.

Lankveld, J.M.G. and J. Lyklema. 1972. J. Colloid Interface Sci., 41:475.

31.

Sato, T. and R. Ruch. 1980. Stabilization of Colloidal Dispersions by Polymer Absorption. New York, NY: Marcel Dekker.

32.

Napper, D.H. 1983. Polymer Stabilization of Colloidal Dispersion. New York, NY: Academic Press.

33.

Chang, S.Y. , T.A. Ring and E.M. Trujillo. 1991. Colloid Polym. Sci. , 269:843.

34.

Baskin, A. , V. Rosilio , G. Albrecht and J. Sunamoto. 1991. J. Colloid Interface Sci., 145:502.

35.

Moellerfeld, J. , W. Prass , H. Ringsdorf , H. Hamazaki and J. Sunamoto. 1986. Biochim. Biophys. Acta., 857:265.