Albumin-heparin microspheres as carriers for cytostatic agents

H.F.M. Cremers, J. Feijen, G. Kwon, Y.H. Bae, S.W. Kim, H.P.J.M. Noteborn, J.G. McVie

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Much work has been done on adriamycin-loaded albumin microspheres (Alb-MS) for chemoembolization [1–4], the rationale being that site-specific drug delivery may increase the therapeutic efficacy of the drug. Alb-Ms are being investigated because of their biocompatibility and because the degradation products of these microspheres are non-toxic. However, these microspheres have some disadvantages (i.e. drug loading during the microsphere preparation, low payloads, large burst effects). These disadvantages can be overcome by the incorporation of heparin (a highly negatively charged mucopolysaccharide). Albumin-heparin microspheres were prepared (i) by crosslinking of soluble albumin and heparin first using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and subsequently glutaraldehyde (Alb-Hep-MS) and (ii) by crosslinking a preformed soluble conjugate of heparin and albumin with glutaraldehyde (Alb-Hep-Conj-MS). Albumin-heparin microspheres could be loaded with adriamycin after microsphere preparation giving payloads of 15–30%. Preliminary in vitro adriamycin release experiments showed that Alb-Hep-Conj-MS exhibit sustained release properties. Furthermore ion-exchange properties could be observed both with Alb-Hep-MS and Alb-Hep-Conj-MS. In vitro and in vivo toxicity experiments with Alb-Hep-MS showed no adverse effects.
Original languageEnglish
Pages (from-to)167-179
JournalJournal of controlled release
Issue number1-3
Publication statusPublished - 1990
Event4th International Symposium on Recent Advances in Drug Delivery Systems 1989 - Salt Lake City, United States
Duration: 21 Feb 198924 Feb 1989
Conference number: 4


  • Chemoembolization
  • Albumin-heparin conjugate
  • Microspheres
  • Ion-exchange hydrogels
  • Adriamycin


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