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Liposomal palmitoyl-L-asparaginase: characterization and biological activity

  • Original Articles
  • Palmitoyl-L-Asparaginase, Liposomes, In Vitro Studies
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Abstract

A new derivative ofL-asparaginase, palmitoyl-L-asparaginase (palmitoyl-L-ASNase), has been incorporated in liposomes. For this purpose we modified the dehydration-rehydration method and optimized the liposomal composition. The pharmacokinetics, toxicity, and in vivo antitumor activity against P1534 lymphoma of different liposomal palmitoyl-L-ASNase formulations were studied. Liposomal encapsulation of palmitoyl-L-ASNase as compared with free palmitoyl-L-ASNase resulted in a prolongation of the blood half-life (from 2.88 h to longer than 23.7 h), abrogation of acute toxicity, and preservation of in vivo antitumor activity.

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References

  1. Allen TM, Chonn A (1987) Large unilamellar liposomes with low uptake into the reticuloendothelial system. FEBS Lett 223:42–46

    Google Scholar 

  2. Asselin BL, Ryan D, Frantz N, Bernal SD, Leavitt P, Sallan SE, Cohen HJ (1989) In vitro and in vivo killing of acute lymphoblastic leukemia cells byL-asparaginase. Cancer Res 49: 4363–4368

    Google Scholar 

  3. Broome JD (1981)L-Asparaginase: discovery and development as a tumor-inhibitory agent. Cancer Treat Rep 65 [Suppl 4]:111–114

    Google Scholar 

  4. Capizzi RL, Cheng Y-C (1981) Treatment of neoplasia with asparaginase. In: Holcenberg JC (ed) Enzymes as drugs. J. Wiley and Sons, New York Chicester Brisbane Toronto Singapore, pp 2–24

    Google Scholar 

  5. Capizzi RL, Handschumacher RE (1982) Asparaginase. In: Holland JF, Frei E III (eds) Cancer medicine. Lea and Febiger, Philadelphia, pp 920–933

    Google Scholar 

  6. Chang TMS (1971) The in vivo effect of semipermeable microcapsules containing L-Asparaginase on 6C3HED lymphosarcoma. Nature 229:117–118

    Google Scholar 

  7. Charles LM Jr, Bono VH Jr (1981) A review of the preclinical antitumor activity and toxicology ofL-asparaginase derived fromE. coli. Cancer Treat Rep 65 [Suppl 4]:39–46

    Google Scholar 

  8. Clarkson B, Krakoff I, Burchenal J, Karnofsky D, Golbey R, Dowling M, Oettgen H, Lipton A (1970) Clinical results of treatment withE. coli L-asparaginase in adults with leukemia, lymphoma and solid tumors. Cancer 25:279–305

    Google Scholar 

  9. Cruz ME, Corvo ML, Jorge JS, Lopes F (1989) Liposomes as carriers of proteins: factors affecting protein encapsulation. In: Lopez-Berenstein G, Fidler IJ (eds) Liposomes in the therapy of infectious diseases and cancer. Alan R. Liss, New York, pp 417–426

    Google Scholar 

  10. Cruz MEM, Gaspar MM, Lopes F, Jorge JS, Perez-Soler R (1993) LiposomalL-asparaginase: in vitro evaluation. Int J Pharm 96: 67–77

    Google Scholar 

  11. Dousset N, Douste-Balazy L (1985) Méthodes de préparation des liposomes. In: Puisieux F, Delattre J (eds) Les liposomes: applications thérapeutiques. Technique et Documentation-Lavoisier, Paris, pp 41–72

    Google Scholar 

  12. Fishman Y, Citri N (1975)L-Asparaginase entrapped in liposomes: preparation and properties. FEBS Lett 60:17–20

    Google Scholar 

  13. Fiske CH, Subbarow J (1925) The colorimetric determination of phosphorus. J Biol Chem 66:375–400

    Google Scholar 

  14. Gabizon A, Papahadjopoulos D (1988) Liposome formulations with prolonged circulation time in blood and enhanced uptake by tumors. Proc Natl Acad Sci USA 85:6949–6953

    Google Scholar 

  15. Gregoriadis G, Leathwood PD, Ryman BE (1971) Enzyme entrapment in liposomes. FEBS Lett 14:95–99

    Google Scholar 

  16. Haskell CM (1981)L-Asparaginase: human toxicology and single agent activity in nonleukemic neoplasms. Cancer Treat Rep 65 [Suppl 4]:57–59

    Google Scholar 

  17. Ho DH, Brown NS, Yen A, Holmes R, Keating M, Abuchowski A, Newman RA, Krakoff IH (1986) Clinical pharmacology of polyethylene glycol-L-asparaginase. Drug Metab Dispos 14:349–352

    Google Scholar 

  18. Jayaram HN, Cooney DA, Jayaram S, Rosenblum L (1974) A simple and rapid method for the estimation ofL-asparaginase in chromatographic and electrophoretic effluents: comparison with other methods. Anal Biochem 59:327–346

    Google Scholar 

  19. Juliano RL (1988) Factors affecting the clearance kinetics and tissue distribution of liposome, microspheres and emulsions. Adv Drug Deliv Rev 2:37–54

    Google Scholar 

  20. King EJ (1932) The colorimetric determination of phosphorus. Biochem J 26:292–297

    Google Scholar 

  21. Kirby C, Gregoriadis G (1984) Dehydration-rehydration vesicles: a simple method for high yield drug entrapment in liposomes. Biotechnology November: 979–984

  22. Land VJ, Sutow WW, Fernbach DJ, Lane DM, Williams TE (1972) Toxicity ofL-asparaginase in children with advanced leukemia. Cancer 30:339–347

    Google Scholar 

  23. Lowry OH, Rosebrough NJ, Farr AL, Randall RT (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275

    Google Scholar 

  24. Martins MBF, Jorge JCS, Cruz MEM (1990) Acylation ofL-asparaginase with total retention of enzymatic activity Biochimie 72: 671–675

    Google Scholar 

  25. Mashburn LT, Wriston JC Jr (1964) Tumor inhibitory effect ofL-asparaginase fromEscherichia coli. Arch Biochem Biophys 105: 450–452

    Google Scholar 

  26. Mori T, Tosa T, Chibata I (1973) Enzymatic properties of microcapsules containing Asparaginase like also to include the last page number of this. Biochim Biophys Acta 321:653–661

    Google Scholar 

  27. Neerunjun ED, Gregoriadis G (1976) Tumour regression with liposome-entrapped asparaginase: some immunological advantages. Biochem Soc Trans 4:133–134

    Google Scholar 

  28. Oettgen HF, Stephenson PA, Schawartz MK, Leeper RD, Tallal L, Tan CC, Clarkson BD, Golbey RB, Krakoff IH, Karnofsky DA, Murphy ML, Burchenal JH (1970) Toxicity ofE. coli L-asparaginase in man. Cancer 25:253–278

    Google Scholar 

  29. Oshawa T, Miura H, Harada K (1985) Evaluation of a new lipsome technique, the freeze-thawing method, usingL-asparaginase as a model drug. Chem Pharm Bull (Tokyo) 33:2916–2923

    Google Scholar 

  30. Roberts J, Prager MD, Bachynsky N (1966) The antitumor activity ofEscherichia coli L-asparaginase. Cancer Res 26:2213–2217

    Google Scholar 

  31. Saito M, Asakura H, Jokaji H, Uotani C, Kumabashiri I, Ito K, Matsuda T (1989) Changes in hemostatic and fibrinolytic proteins in patients receivingL-asparaginase therapy. Am J Hematol 32: 20–23

    Google Scholar 

  32. Wang C-H, Smith RL (1975) Lowry determination of the protein in the presence of Triton X-100. Anal Biochem 63:414–417

    Google Scholar 

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Jorge, J.C.S., Perez-Soler, R., Morais, J.G. et al. Liposomal palmitoyl-L-asparaginase: characterization and biological activity. Cancer Chemother. Pharmacol. 34, 230–234 (1994). https://doi.org/10.1007/BF00685082

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  • DOI: https://doi.org/10.1007/BF00685082

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