There exists a need to deliver high concentrations of certain substances specifically to sites of fibrin formation in vivo, e.g., inflammatory sites, solid tumors, bacterial abscesses, atherosclerotic plaques, thrombi, etc. Phospholipid liposomes can be loaded with various substances and, thus, liposomes are ideally suited for delivering high concentrations of materials to sites of fibrin formation. We reasoned that if functional fibrinogen could be incorporated into the liposomal bilayers, then such fibrinogen-coated liposomes might be incorporated into growing fibrin matrices. To test this hypothesis, we first developed a method for coating liposomes with functional fibrinogen. Fibrinogen-coated liposomes prepared in this fashion are readily incorporated into fibrin clots in vitro. We tested whether these liposomes accumulate at sites of fibrin formation in vivo. For this purpose, a well-characterized inflammatory model was used. In this model, a localized, fibrin-rich inflammatory response is initiated by injecting trehalose 6,6'-dimycolate-coated, polystyrene-divinylbenzene beads into a footpad of a mouse. To follow the localization of liposomes into the inflamed foot, [3H]inulin was encapsulated within liposomes. Fibrinogen-coated, [3H]inulin-containing liposomes and, as a control, fibrinogen-free [3H]inulin-containing liposomes were injected intravenously into mice that had been administered beads 24 hr earlier. Six hours after injecting liposomes, animals were sacrificed, and the radioactivity in their feet was determined. The radioactivity associated with the inflamed foot was compared with that in the untreated foot on a radioactivity per unit mass basis. For fibrinogen-coated liposomes, the accumulated radioactivity was ∼ 3x's that which accumulated when using fibrinogen-free liposomes. Thus, when compared to conventional liposomes, fibrinogen-coated liposomes significantly improve the delivery of [3H]inulin to a fibrin-rich inflammatory site. We propose that fibrinogen-coated liposomes represent a novel means for targeting drugs to any site of fibrin deposition.
|Original language||English (US)|
|State||Published - Mar 20 1998|
ASJC Scopus subject areas
- Molecular Biology