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Biotechnology and Applied Biochemistry (1999) 29, (251–261) (Printed in Great Britain)

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Accumulation of fibrinogen-coated microparticles at afibrin(ogen)-rich inflammatory site

Ashley P. DeAnglis¹, Michael D.Fox and Gregory S. Retzinger

Department of Pathology and Laboratory Medicine, Universityof Cincinnati, Cincinnati, OH 45267-0529, U.S.A.

Abbreviations used: LHF, left hind foot; RHF, right hind foot; NIH, National Institutes of Health; TDM, trehalose 6,6´-dimycolate; RAI, relative accumulation index.

¹ To whom correspondence should be sent.

We have developed methods for coating with fibrinogen both liposomes and microscopic droplets of olive oil. Because the fibrinogen bound to them is functional in the classic sense of fibrin gelation, the coated microparticles may have potential as vehicles for the targeted delivery of various molecules to sites of fibrin(ogen) deposition in vivo. So that we could assess directly this potential, we first established a method for eliciting reproducibly a focal, fibrin(ogen)-rich, inflammatory lesion in a hind footpad of mice. We then monitored the tissue distribution of fibrinogen-coated microparticles following their injection into the tail vein of mice bearing this well-defined lesion. As happens with most microparticles following their intravenous administration, liposomes and oil droplets, whether coated with fibrinogen or not, accumulate rapidly in the liver and spleen of treated animals. Indeed, in the case of oil droplets, accumulation of fibrinogen-coated microparticles in those organs and in the lungs is even greater than that of fibrinogen-free microparticles. However, as distinct from fibrinogen-free liposomes and oil droplets, fibrinogen-coated microparticles also accumulate in the inflamed hind footpad. We conclude that fibrinogen-coated liposomes and oil droplets do have potential as vehicles for delivering molecules to sites of fibrin(ogen) deposition in vivo.

Received 3 February 1999; accepted 25 February 1999

Portland Press Ltd © 1999