title: Intrapericardial delivery of gelfoam enables the targeted delivery of Periostin peptide after myocardial infarction by inducing fibrin clot formation.
abstract: BACKGROUND
  Administration of a recombinant peptide of Periostin (rPN) has recently been shown to stimulate cardiomyocyte proliferation and angiogenesis after myocardial infarction (MI) [1]. However, strategies for targeting the delivery of rPN to the heart are lacking. Intrapericardial administration of drug-eluting hydrogels may provide a clinically viable strategy for increasing myocardial retention, therapeutic efficacy, and bioactivity of rPN and to decrease systemic re-circulation.
  
  
  RESULTS
  We investigated the ability of intrapericardial injections of drug-eluting hydrogels to deliver and prolong the release of rPN to the myocardium in a large animal model of myocardial infarction. Gelfoam is an FDA-approved hemostatic material commonly used in surgery, and is known to stimulate fibrin clot formation. We show that Gelfoam disks loaded with rPN, when implanted within the pericardium or peritoneum of mammals becomes encapsulated within a non-fibrotic fibrin-rich hydrogel, prolonging the in vitro and in vivo release of rPN. Administration into the pericardial cavity of pigs, following a complete occlusion of the left anterior descending artery, leads to greater induction of cardiomyocyte mitosis, increased cardiomyocyte cell cycle activity, and enhanced angiogenesis compared to direct injection of rPN alone.
  
  
  CONCLUSIONS
  The results of this study suggest that intrapericardial drug delivery of Gelfoam, enhanced by triggered clot formation, can be used to effectively deliver rPN to the myocardium in a clinically relevant model of myocardial infarction. The work presented here should enhance the translational potential of pharmaceutical-based strategies that must be targeted to the myocardium.
authors.affiliation: Department of Cardiology, Children's Hospital Boston, Boston, Massachusetts, United States of America. brian.polizzotti@childrens.harvard.edu
authors.forename: Brian D
authors.initials: BD
authors.lastname: Polizzotti
authors.forename: Shima
authors.initials: S
authors.lastname: Arab
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kühn
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000494:pharmacology*; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D003692:Delayed-Action Preparations / Q000494:pharmacology; D005260:Female; D005337:Fibrin / Q000378:metabolism; D005781:Gelatin Sponge, Absorbable / Q000494:pharmacology*; D006490:Hemostatics; D006801:Humans; D051379:Mice; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology*; D010496:Pericardium / Q000378:metabolism / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology; D013552:Swine
chemical_list: D015815:Cell Adhesion Molecules; D003692:Delayed-Action Preparations; D006490:Hemostatics; C512835:POSTN protein, human; D010455:Peptides; D011994:Recombinant Proteins; D005337:Fibrin