title: Oral delivery of low molecular weight heparin by polyaminomethacrylate coacervates.
abstract: OBJECTIVE
  Oral bioavailability of low molecular weight heparin (LMWH) can be achieved by several advanced drug delivery approaches. Here, a new preparation method for coacervates (CAs) using non-toxic polyethylene glycol derivates was developed.
  
  
  METHODS
  LMWH were coacervated with polyaminomethacrylates (Eudragit® RL or RS) using polyethylene glycol (PEG) derivatives as non-toxic solvents. CAs were analyzed for their physicochemical properties and pharmacokinetic parameters were determined for different formulations in rabbits.
  
  
  RESULTS
  CAs from both polymer types using various PEGs were of irregular shape and had particle sizes of around 40 μm, encapsulation efficiencies of >90%, and complete LMWH in vitro release was obtained within 2 h. In vivo, oral Absorption at doses of 300 IU/kg was rather low (F < 2.5%) while dose increase resulted in a maximum at 600 IU/kg (FRL: 6.0 ± 1.2%; FRS: 5.8 ± 2.5%) and 1,200 IU/kg did not result in higher bioavailability (FRL: 4.6 ± 0.4%; FRS: 4.1 ± 0.8%). CAs were applicable to various LMWH types where the oral availability decreased in the order fondaparinux>enoxaparin>nadroparin>certoparin depending mainly on the molecular weight.
  
  
  CONCLUSIONS
  CAs prepared by an organic solvent-free method allowed the oral delivery of LMWHs. The therapeutic efficiency and the simple and solvent-free manufacturing process underlines the high potential of this new preparation method.
authors: Laboratory of Pharmaceutical Technology and Biopharmaceutics, University of Bonn, Bonn, Germany.
authors: Angela
authors: A
authors: Viehof
authors: Alf
authors: A
authors: Lamprecht
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D000284:Administration, Oral; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage*; D004337:Drug Carriers / Q000737:chemistry*; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011817:Rabbits
chemical_list: D000180:Acrylic Resins; D000925:Anticoagulants; D004337:Drug Carriers; D006495:Heparin, Low-Molecular-Weight; C050528:Eudragit RS; D011092:Polyethylene Glycols
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