YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Pharmacokinetics, Cell Toxicity, Antitumor Activity and Spleen/Blood Cell Toxicity of Aclarubicin-entrapped Liposomes

리포좀에 봉입된 아클라루비신의 약물동태, 세포독성, 항암효과 및 비장/혈구 세포독성

  • Published : 1998.06.01

⟨ Previous Next ⟩

Abstract

Aclarubicin(ACL)-entrapped freeze dried liposomes were prepared using Microfludizer to attain a sustained release at targeted organs in a prolonged time so that it can reduce th e side effect and maximize the therapeutic effect. The freeze-dried liposomes were evaluated for pharmacokinetics, antitumor activity against Sarcoma 180, cytotoxicity against L1210 and A549 tumor cells, spleen toxicity and myelosuppressive action. The AUC0->8hr values were 122+/-42, 382+/-140, 419+/-171, 835+/-206 and 443+/-309mcg min/ml for free ACL. ACL-liposome formulation I, II, III and IV, respectively. Cytotoidcity of ACL-entrapped liposomes against L1210 and A549 tumor cells was 2-4 times higher than that of free aclarubicin. ACL-liposome formulation I(PC/CHOL/TA) showed the most potent antitumor activity against Sarcoma 180 in mice. The loss of body weight was much smaller with ACL-entrapped liposomes than free ACL after I.p. injection at a dose of 2 mg/kg/day. Compared to free ACL, ACL-entrapped liposomes expressed a lower and delayed spleen toxicity up to 5th day after I.v. administration. Myelosupperssion seemed to be lower with ACL-entrapped liposome of PC/PC-hydrate/CHOL/TA (formulation III) than free aclarubicin.

Keywords

References

  1. Chem. Pharm, Bull. v.33 Modification of the release rate of aclarubicin from polylactic acid microspheres by using additives Juni, K.;Ogata, J.;Matsui, N.;Kubota, M.;Nakano, M.
  2. Liposome Technology v.1 Frokjaer, S.;Hjorth, E. L.;Worts, O.;G. Gregoriadis(ed.)
  3. Biochim. Biophys. Acta. v.819 Oxidation of biological membranes and its inhibition, free radical chain oxidation of erythrocyte ghost membranes by oxygen Yamamoto, Y.;Niki, E.;Eguchi, J.;Kamiya, Y.;Shimasaki, H.
  4. Science v.223 Preservation of membranes in anhydrobiotic organisms: The role of trehalose Crowe, J. H.;Crowe, L. M.
  5. Biochym. Biophys. Acta v.897 Stabilization of small unilamellar phospholipid vesicles during spray-drying Helmut, H.;Strauss, G.
  6. Chem, Pharm. Bull. v.32 A novel method for preparing liposomes with a high capacity to encapsulate proteinous drugs : Freeze-drying method Ohasawa, T.;Miura, H.;Harada, K.
  7. Chem. Pharm, Bull. v.36 Liposomal sustained-release delivery systems for intravenous injection Ⅱ. Design of liposome carriers and blood disposition of lipophilic mitomycin C prodrug-bearing liposome Tokunaga, Y.;Iwasa, T.;Fusisaki, J.;Sawai, S.;Kagayma, A.
  8. Chem. Pharm. Bull. v.36 Liposomal sustained-release delivery systems for intravenous injection Ⅲ. Antitumor activity of lipophilic mitomycin C prodrug-bearing liposomes Tokunaga, Y.;Iwasa, T.;Fusisaki, J.;Sawai, S.;Kagayma, A.
  9. Chem. Pharm. Bull. v.36 Liposomal sustained-release delivery systems for intravenous injection Ⅳ. Antitumor activity of newly synthesized lipophilic 1-β-d-arabinofuranosyl-cytosine prodrug-bearing liposomes Tokunaga, Y.;Iwasa, T.;Fusisaki, J.;Sawai, S.;Kagayma, A.
  10. japan patent open. Kurone, M.;Sasaki, Y.;Yokohama, H.;Chiba, T.;Fujii, S.
  11. Biol. Pharm. Bull. v.17 Effects of fluidity and vesicle size on antitumor activity and myelosuppressive activity of liposomes loaded with daunorubicin Nagayasu, A.;Shimooka, T.;Kinouchi, Y.;Uchiyama, K.;Takeichi, Y.;Kiwada, H.
  12. Liposomes as delivery system for doxorubicin in cancer chemotherapy Storm,G.;van Hoesel, Q. G. C. M.;deGroot, G.;Kop, W.;Kruizinga, W.;Hillen, F. C.;G. Storm(ed.)
  13. Cancer Res. v.45 Pharmacological, toxicological and therapeutic evaluation in mice of doxorubicin entrapped in cardiolipin liposomes Rahman, A.;White, G.;More, N.;Schein, P. S.
  14. Int. J. Cancer v.37 Treatment of murine L1210 lymphoid leukemia and melanoma B16 with lipophilic cytosine arabinoside prodrugs incorporated into unilamellar liposomes Rubas, W.;Supersaxo, A.;Weder, H. G.;Hartmann, H. R.;Hengartner, H.;Schott, H.;Schwendener, R.