title: A novel hemostatic delivery device for thrombin: biodegradable poly(D,L-lactide-co-glycolide) 50:50 microspheres.
abstract: Topical thrombins are locally active hemostatic agents that can be used to minimize blood loss during any surgery. The aim of this study was to design and investigate a thrombin-containing biodegradable hemostyptic device with an optimized drug release profile to promote local blood clot formation. It is effective with ongoing systemic antithrombotic therapy and can be used in all types of bone-related surgery, for example, in dental surgery. Thrombin-loaded poly(D,L-lactide-co-glycolide) microspheres were synthesized by means of complex (w/o/w) emulsion evaporation method. The resulting enzyme activity of the serine-protease thrombin was verified by the specific chromogenic substrate S-2238. The thrombin release profile depended on four factors: (1) thrombin dosage, (2) polymer concentration in the o-phase, (3) phase quotient w1:0 in the primary emulsion, and (4) the addition of pore-introducing agents. A collagenous sponge containing thrombin-loaded microspheres by means of lyophilization was developed. The impact of several production factors of the (w1/o/w2) solvent evaporation method to optimize thrombin encapsulation, morphology of the spheres, and desired drug release profile have been investigated. The in vitro thrombin release was dependent on the polymer-to-oil phase ratio, the polymer concentration, and the type of solvent and polymer. The porosity of the spheres and release rate of the active agent were enhanced by increasing the inner aqueous w1 phase. With this study, a new biodegradable hemostyptic device could be verified and established for a potentially safe and locally controlled thrombin release to manage postsurgical hemorrhage in patients undergoing anticoagulant therapy.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University Hospital Aachen, Aachen, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Smeets
authors.forename: Frank
authors.initials: F
authors.lastname: Gerhards
authors.forename: Jamal M
authors.initials: JM
authors.lastname: Stein
authors.forename: Jamal
authors.initials: J
authors.lastname: Stein
authors.forename: Rui Miguel Pereira
authors.initials: RM
authors.lastname: Paz
authors.forename: Stephan
authors.initials: S
authors.lastname: Vogt
authors.forename: Christoph
authors.initials: C
authors.lastname: Pautke
authors.forename: Jochen
authors.initials: J
authors.lastname: Weitz
authors.forename: Andreas
authors.initials: A
authors.lastname: Kolk
mesh_terms: D020341:Absorbable Implants; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D006490:Hemostatics / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000737:chemistry*; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012997:Solvents; D013917:Thrombin / Q000737:chemistry / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D006490:Hemostatics; D012997:Solvents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D013917:Thrombin