Archives of Pharmacal Research

, Volume 8, Issue 3, pp 159–168 | Cite as

Development of specific organ-targeting drug delivery system I: Physico-pharmaceutical characteristics of thermally denatured albumin microspheres containing cytarabine

  • Chong-Kook Kim
  • Eun Ju Jeong
  • Ji Sun Yang
  • Seung Hwan Kim
  • Yang Bae Kim
Original Articles


In attempt to develop a drug delivery system using serum albumin microspheres, bovine serum albumin microspheres containing antitumor agent, cytarabine, were prepared. The shape, surface characteristics, size distribution, behavior ofin vitro distribution, drug release behavior, and degradation of albumin microspheres in animal liver tissue homogenate and proteolytic enzyme were investigated.

The shape of albumin microspheres was spherical and the surface was smooth and compact. The size distribution of the albumin microspheres was affected by dispersion forces during emulsification and albumin concentration. Distribution of albumin microspheres after intravenous administration in rabbit was achieved immediately.In vitro, albumin microsphere matrix was so hard that it retained most of cytarabine except initial burst during the first 10 minutes, and the level of drug release during the initial burst was affected by heating temperature, drug/albumin concentration ratio and size distribution. After drug release test, the morphology of albumin microspheres was not changed. Albumin microsphere matrix was degraded by the rabbit liver tissue homogenate and proteolytic enzyme. The degree of degradation was affected by heating temperature.


Bovine serum albumin Drug delivery system Cytarabine Cottonseed oil Size distribution Surface characteristics of albumin microspheres Preparation of albumin microspheres Drug release from albumin microspheres Distribution of albumin microspheres after I.V. administration in rabbit 


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Literature Cited

  1. 1).
    Zolle, I., Rhodes, B. A. and Wagner, Jr., N. H.: Preparation of metabolizable radioactive human serum microspheres for studies of the circulation.Int. J. Appl. Rad. Iso.,21, 155 (1970).CrossRefGoogle Scholar
  2. 2).
    Cornell, R. P. and Saba, T. M.: Humoral control of colloid clearance by reticuloendothelial system in dogs.Am. J. Physiol.,225, 1300 (1973).PubMedGoogle Scholar
  3. 3).
    Scheffel, U., Rhodes, B. A., Natarajan, J. K. and Wagner, Jr., N. H.: Albumin microspheres for study of the reticuloendothelial system.J. Nucl. Med.,13, 498 (1972).PubMedGoogle Scholar
  4. 4).
    Kramer, P. A.: Albumin microspheres as vehicles for achieving specificity in drug delivery.J. Pharm. Sci.,63, 1646 (1974).PubMedCrossRefGoogle Scholar
  5. 5).
    Kramer, P. A. and Burnstein, T.: Phagocytosis of microspheres containing an anticancer agent by tumor cellsin vitro.Life Sci.,19, 515 (1976).PubMedCrossRefGoogle Scholar
  6. 6).
    Sugibayashi, K., Morimoto, Y., Nadai, T. and Kato, Y.: Drug-carrier property of albumin microspheres in chemotherapy. II. Preparation and tissue distribution in mice of microsphere-entrapped 5-Fluorouracil.Chem. Pharm. Bull.,27, 204 (1979).PubMedGoogle Scholar
  7. 7).
    Sugibayashi, K., Akimoto, M., Morimoto, Y., Nadai, T. and Kato, Y., Drug-carrier property of albumin microspheres in chemotherapy. III. Effect of microsphere-entrapped 5-fluorouracil on Ehrlich ascites carcinoma in mice.J. Pharm. Dyn.,2, 350 (1979).Google Scholar
  8. 8).
    Morimoto, Y., Akimoto, M., Sugibayashi, K., Nadai, T. and Kato, Y.: Drug-carrier property of albumin microspheres in chemotherapy. IV. Antitumor effect of single-shoot or multiple-shot administration of microsphere-entrapped 5-flluorouracil on Ehrlich Ascites or solid tumor in mice.Chem. Pharm. Bull.,28, 3087 (1980).PubMedGoogle Scholar
  9. 9).
    Morimoto, Y., Sugibayashi, K. and Kato, Y., Drug-carrier property of albumin microspheres in chemotherapy. V. Antitumor effect of microsphere-entrapped adriamycin on liver metastasis of AH 7974 cells in rats.Chem. Pharm. Bull.,29, 1433 (1981).PubMedGoogle Scholar
  10. 10).
    Widder, K. J. and Senyei, A. E.: Intravascularly-administrable, magnetically-localizable carrier.U. S. pat. 4, 247, 406 (1981).Google Scholar
  11. 11).
    Widder, K. J., Senyei, A. E. and Ranney, D. F.:In vitro release of biologically active adriamycin by magnetically responsive albumin microspheres. Cancer Research,40, 3512 (1980).PubMedGoogle Scholar
  12. 12).
    Widder, K. J., Morris, R. M., Poore, G., Howard, Jr., D. and Senyei, A. E.: Tumor remission in Yoshida sarcoma-bearing rats by selective targeting of magnetic albumin microspheres containing doxorubicin.Proc. Natl. Acad. Sci., USA,78, 579 (1981).PubMedCrossRefGoogle Scholar
  13. 13).
    Fushimi, H., Shibata, M. and Tarui, S.: Glycosidase activities in the liver and kidney of hereditary diabetic mice.J. Biochem.,87, 941 (1980).PubMedGoogle Scholar

Copyright information

© The Pharmaceutical Society of Korea 1985

Authors and Affiliations

  • Chong-Kook Kim
    • 1
  • Eun Ju Jeong
    • 1
  • Ji Sun Yang
    • 1
  • Seung Hwan Kim
    • 1
  • Yang Bae Kim
    • 1
  1. 1.College of PharmacySeoul National UniversitySeoulKorea

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