Adriamycin-loaded albumin-heparin conjugate microspheres for intraperitoneal chemotherapy


Cremers, H.F.M. and Seymour, L.W. and Lam, K. and Los, G. and Vugt, M. van and Kwon, G. and Bae, Y.H. and Kim, S.W. and Feijen, J. (1994) Adriamycin-loaded albumin-heparin conjugate microspheres for intraperitoneal chemotherapy. International journal of pharmaceutics, 110 (2). pp. 117-125. ISSN 0378-5173

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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.
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Copyright:© 1994 Elsevier Science
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Metis ID: 105316