Adriamycin-loaded albumin-heparin conjugate microspheres for intraperitoneal chemotherapy

Harry Cremers, H.F.M. Cremers, L.W. Seymour, K. Lam, G. Los, M. van Vugt, G. Kwon, Y.H. Bae, S.W. Kim, Jan Feijen

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Abstract

Adriamycin-loaded albumin-heparin conjugate microspheres (ADR-AHCMS) were evaluated as possible intraperitoneal (i.p.) delivery systems for site-specific cytotoxic action. The biocompatibility of the microspheres after intraperitoneal injection was tested first. 1 day after i.p. administration of empty as well as drug-loaded AHCMS to male Balb/c mice, only a moderate increase in i.p. neutrophils was measured. 3 days after injection neutrophil levels were comparable with the controls. No significant increases in the numbers of other cell types were observed, indicating an acute inflammatory response which can be considered to be mild. Antitumour efficacy was tested in an L1210 tumour-bearing mouse model and in a CC531 tumour-bearing rat model. The use of ADR-AHCMS leads to longer survival times of mice and improved tumour growth delay in rats, as compared with untreated controls and free drug treated animals. In both animal models higher adriamycin doses were initially tolerated if the drug was formulated in microspheres, although long-term adriamycin toxicity effects were evident in all treated groups. Doses and dosage schedules may be optimized to further reduce the toxic effects of the drug.
Original languageUndefined
Pages (from-to)117-125
JournalInternational journal of pharmaceutics
Volume110
Issue number2
DOIs
Publication statusPublished - 1994

Keywords

  • IR-9744
  • METIS-105316

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