title: Controlled release of substances bound to fibrin-anchors or of DNA.
abstract: Fibrin sealants have been proposed as depot matrices for substances due to their biocompatibility, advantageous biological properties, and widespread use in wound healing. This study showed possibilities for a continuous and controlled release of pharmaceutically active substances out of a fibrin matrix. Substances of interest were linked to naturally occuring fibrin-anchors, (i) thrombin, (ii) fibronectin, and (iii) DNA. Fibronectin and thrombin bind fibrin by a specific binding moiety and DNA by charge. Fibrin clots were prepared from Tisseel Fibrin Sealant (Baxter AG, Vienna) by mixing 100 mg/ml fibrinogen, the substance of interest, and 4 U/ml of thrombin. Chemical crosslinking of proteins was performed with EDC using standard reaction conditions. Modification of proteins with biotin and PPACK was performed with N-hydroxysuccinimid activated compounds. With fibrin-anchors pharmaceutically active substances, i.e., tumor necrosis factor (TNF), albumin, and plasmid-DNA, were continously released over 10 days. In conclusion, the naturally occuring proteins fibronectin and thrombin with a fibrin binding moiety or DNA can be used as fibrin-anchors.
authors.affiliation: Ludwig Boltzmann Institute for Experimental, Clinical Traumatology/AUVA Research Center, Vienna, Austria. tatjana.morton@lbitrauma.org
authors.forename: T J
authors.initials: TJ
authors.lastname: Morton
authors.forename: W
authors.initials: W
authors.lastname: Fürst
authors.forename: M
authors.initials: M
authors.lastname: van Griensven
authors.forename: H
authors.initials: H
authors.lastname: Redl
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000737:chemistry; D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000276:immunology; D001682:Biological Availability; D002417:Cattle; D045304:Cytochromes c / Q000008:administration & dosage / Q000493:pharmacokinetics; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations / Q000138:chemical synthesis / Q000737:chemistry*; D005337:Fibrin / Q000737:chemistry*; D005340:Fibrinogen / Q000737:chemistry; D005353:Fibronectins / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry; D010957:Plasmids / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D012709:Serum Albumin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D019809:Streptavidin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D013917:Thrombin / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics; D014568:Urokinase-Type Plasminogen Activator / Q000737:chemistry; D001616:beta-Galactosidase / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D000906:Antibodies; D003692:Delayed-Action Preparations; D005353:Fibronectins; D004364:Pharmaceutical Preparations; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha; D005337:Fibrin; D005340:Fibrinogen; D045304:Cytochromes c; D004247:DNA; D019809:Streptavidin; D001616:beta-Galactosidase; D013917:Thrombin; C050815:phenylalanyl-prolyl-arginine chloromethyl ketone-thrombin; D014568:Urokinase-Type Plasminogen Activator