Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1985 Dec;52(6):841–848. doi: 10.1038/bjc.1985.267

Poly-L-aspartic acid as a carrier for doxorubicin: a comparative in vivo study of free and polymer-bound drug.

G Pratesi, G Savi, G Pezzoni, O Bellini, S Penco, S Tinelli, F Zunino
PMCID: PMC1977272  PMID: 4074638

Abstract

The synthetic polypeptide, poly-L-aspartic acid (PAA, mol. wt = 20,000) has been used as a macromolecular carrier for doxorubicin. The drug may be released in vivo through hydrolysis of the ester linkage formed between the carboxyl groups of the polymer and the drug side chain. PAA has been found to be a suitable carrier since it is a soluble, biodegradable, multivalent and nontoxic polymer. The toxicity and the therapeutic efficacy of free and polymer-linked doxorubicin have been evaluated in normal and tumour-bearing mice, using a variety of experimental tumour systems. In studies on single and multiple drug administration, the results indicated that the polymeric derivative of doxorubicin had approximately 3-fold lower toxicity than did free drug. In addition, the severity of specific toxic effects, including cardio- and vesicant toxicity, were appreciably reduced following conjugation to PAA. The doxorubicin-PAA conjugate gave similar or rather greater therapeutic effects than free drug at less toxic doses. This effect, more evident in the highly sensitive tumours, suggests an improvement of the therapeutic index of the polymer-linked drug.

Full text

PDF
841

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bertazzoli C., Bellini O., Magrini U., Tosana M. G. Quantitative experimental evaluation of adriamycin cardiotoxicity in the mouse. Cancer Treat Rep. 1979 Nov-Dec;63(11-12):1877–1883. [PubMed] [Google Scholar]
  2. Casazza A. M., Savi G., Pratesi G., Di Marco A. Antitumor activity in mice of 4'-deoxydoxorubicin in comparison with doxorubicin. Eur J Cancer Clin Oncol. 1983 Mar;19(3):411–418. doi: 10.1016/0277-5379(83)90140-2. [DOI] [PubMed] [Google Scholar]
  3. Di Marco A., Lenaz L., Casazza A. M., Scarpinato B. M. Activity of adriamycin (NSC-123127) and daunomycin (NSC-82151) against mouse mammary carcinoma. Cancer Chemother Rep. 1972 Apr;56(2):153–161. [PubMed] [Google Scholar]
  4. Gregoriadis G. Targeting of drugs: implications in medicine. Lancet. 1981 Aug 1;2(8240):241–246. doi: 10.1016/s0140-6736(81)90486-4. [DOI] [PubMed] [Google Scholar]
  5. Jenkins J., Corden B. J. Vesicant activity of chemotherapeutic agents. Cancer Treat Rep. 1983 Apr;67(4):409–409. [PubMed] [Google Scholar]
  6. Kaye S. B. Liposomes--problems and promise as selective drug carriers. Cancer Treat Rev. 1981 Mar;8(1):27–50. doi: 10.1016/s0305-7372(81)80004-7. [DOI] [PubMed] [Google Scholar]
  7. Lenaz L., Page J. A. Cardiotoxicity of adriamycin and related anthracyclines. Cancer Treat Rev. 1976 Sep;3(3):111–120. doi: 10.1016/s0305-7372(76)80018-7. [DOI] [PubMed] [Google Scholar]
  8. Levi-Schaffer F., Bernstein A., Meshorer A., Arnon R. Reduced toxicity of daunorubicin by conjugation to dextran. Cancer Treat Rep. 1982 Jan;66(1):107–114. [PubMed] [Google Scholar]
  9. Myers C. E., Collins J. M. Pharmacology of intraperitoneal chemotherapy. Cancer Invest. 1983;1(5):395–407. doi: 10.3109/07357908309048508. [DOI] [PubMed] [Google Scholar]
  10. Talmadge J. E., Donovan P. A., Hart I. R. Inhibition of cellular division of a murine macrophage tumor by macrophage-activating agents. Cancer Res. 1982 May;42(5):1850–1855. [PubMed] [Google Scholar]
  11. Talmadge J. E., Key M. E., Hart I. R. Characterization of a murine ovarian reticulum cell sarcoma of histiocytic origin. Cancer Res. 1981 Apr;41(4):1271–1280. [PubMed] [Google Scholar]
  12. Tarnowski G. S., Ralph P., Stock C. C. Sensitivity to chemotherapeutic and immunomodulating agents of two mouse lymphomas and of a macrophage tumor. Cancer Res. 1979 Oct;39(10):3964–3967. [PubMed] [Google Scholar]
  13. Zunino F., Giuliani F., Savi G., Dasdia T., Gambetta R. Anti-tumor activity of daunorubicin linked to poly-L-aspartic acid. Int J Cancer. 1982 Oct 15;30(4):465–470. doi: 10.1002/ijc.2910300413. [DOI] [PubMed] [Google Scholar]
  14. Zunino F., Savi G., Giuliani F., Gambetta R., Supino R., Tinelli S., Pezzoni G. Comparison of antitumor effects of daunorubicin covalently linked to poly-L-amino acid carriers. Eur J Cancer Clin Oncol. 1984 Mar;20(3):421–425. doi: 10.1016/0277-5379(84)90091-9. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES