Ideal Amphipathic Peptdes Coupled to Nanofibrous Micropheres Reduce Hemorrhage In Vivo

Abstract 2204

We have previously shown that ideal amphipathic peptides (IAP) composed simply of leucine and lysine residues can augment the function of the procoagulant enzyme, factor IX in vitro (Biochem J 2008). We have also shown that surface attachment of IAP can promote hemostasis and reduce bleeding in vivo. We extend these observations by coupling IAPs to a nanomaterial called nanofibrousmicrospheres (NFM). NFMs have a large surface area to volume ratio thereby providing greater surface area and better access to bleeding surfaces especially those that are internal and difficult to reach. Initially we demonstrate, by fluorescently labeling IAP with dansyl chloride, that IAP attaches to NFM. When free dansyl IAP is added to NFM, 90% binds to the surface of NFM via a non-covalent linkage. Both a murine liver laceration model and a murine tail transection model were established to evaluate the in vivo hemostatic properties of IAP attached to NFM (IAP-NFM). In a murine liver laceration model, where the liver is cut with a Surgicutt template, application of IAP-NFM significantly reduces bleeding times by 40% as compared to application of NFM alone (p<0.01), or no treatment (p<0.01). As well, comparison of IAP-NFM to QuikClot, a current commercially used product for control of hemorrhagic injuries, show a greater reduction in bleeding times after application of IAP-NFM as compared to QuikClot. In addition, histologic examination of the lacerated liver after treatment reveal that IAP-NFM elicited little tissue injury whereas widespread hepatocyte injury was caused by QuikClot, due to its known exothermic reaction on tissue. The bleeding time in a murine tail transection model was also reduced by approximately 30% by IAP-NFM, as compared to NFM alone (p<0.01), or no treatment (p<0.05). In conclusion, IAP attachment to NFM results in a biocompatible material that is procoagulant and can promote hemostasis in vivo with the advantage that it exhibits little tissue injury after its application.