title: Liposome encapsulated berberine treatment attenuates cardiac dysfunction after myocardial infarction.
abstract: Inflammation is a known mediator of adverse ventricular remodeling after myocardial infarction (MI) that may lead to reduction of ejection fraction and subsequent heart failure. Berberine is a isoquinoline quarternary alkaloid from plants that has been associated with anti-inflammatory, anti-oxidative, and cardioprotective properties. Its poor solubility in aqueous buffers and its short half-life in the circulation upon injection, however, have been hampering the extensive usage of this natural product. We hypothesized that encapsulation of berberine into long circulating liposomes could improve its therapeutic availability and efficacy by protecting cardiac function against MI in vivo. Berberine-loaded liposomes were prepared by ethanol injection and characterized. They contained 0.3mg/mL of the drug and were 0.11μm in diameter. Subsequently they were tested for IL-6 secretion inhibition in RAW 264.7 macrophages and for cardiac function protection against adverse remodeling after MI in C57BL/6J mice. In vitro, free berberine significantly inhibited IL-6 secretion (IC50=10.4μM), whereas encapsulated berberine did not as it was not released from the formulation in the time frame of the in vitro study. In vivo, berberine-loaded liposomes significantly preserved the cardiac ejection fraction at day 28 after MI by 64% as compared to control liposomes and free berberine. In conclusion, liposomal encapsulation enhanced the solubility of berberine in buffer and preserves ejection fraction after MI. This shows that delivery of berberine-loaded liposomes significantly improves its therapeutic availability and identifies berberine-loaded liposomes as potential treatment of adverse remodeling after MI.
authors.affiliation: Department of Biomaterials Science and Technology, University of Twente, Enschede, Drienerlolaan 5, 7522 NB Enschede, The Netherlands.
authors.forename: Iris E
authors.initials: IE
authors.lastname: Allijn
authors.affiliation: Department of Pharmacy, National University of Singapore, Science Drive 2, 117543, Singapore; Department of Pharmaceutics, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
authors.forename: Bertrand M S
authors.initials: BMS
authors.lastname: Czarny
authors.affiliation: Department of Surgery, YLL School of Medicine, National University of Singapore, Singapore; Cardiovascular Research Institute (CVRI), National University Heart Centre Singapore (NUHCS) and National University Health System (NUHS), 117599, Singapore.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Surgery, YLL School of Medicine, National University of Singapore, Singapore; Cardiovascular Research Institute (CVRI), National University Heart Centre Singapore (NUHCS) and National University Health System (NUHS), 117599, Singapore.
authors.forename: Suet Yen
authors.initials: SY
authors.lastname: Chong
authors.affiliation: Department of Experimental Molecular Imaging, University Clinic RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
authors.forename: Marek
authors.initials: M
authors.lastname: Weiler
authors.affiliation: Department of Biomaterials Science and Technology, University of Twente, Enschede, Drienerlolaan 5, 7522 NB Enschede, The Netherlands.
authors.forename: Acarilia Eduardo
authors.initials: AE
authors.lastname: da Silva
authors.affiliation: Department of Biomaterials Science and Technology, University of Twente, Enschede, Drienerlolaan 5, 7522 NB Enschede, The Netherlands; Department of Experimental Molecular Imaging, University Clinic RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
authors.forename: Josbert M
authors.initials: JM
authors.lastname: Metselaar
authors.affiliation: National Heart Centre Singapore, Singapore General Hospital, Duke-National University, Hospital Drive 5, 169609, Singapore; Department of Cardiology, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands.
authors.forename: Carolyn Su Ping
authors.initials: CSP
authors.lastname: Lam
authors.affiliation: Department of Pharmacy, National University of Singapore, Science Drive 2, 117543, Singapore.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Pastorin
authors.affiliation: Department of Surgery, YLL School of Medicine, National University of Singapore, Singapore; Vascular Surgery & Experimental Cardiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands; Interuniversity Cardiology Institute of the Netherlands (ICIN), PO Box 19258, 3501 DG Utrecht, The Netherlands.
authors.forename: Dominique P V
authors.initials: DPV
authors.lastname: de Kleijn
authors.affiliation: Department of Biomaterials Science and Technology, University of Twente, Enschede, Drienerlolaan 5, 7522 NB Enschede, The Netherlands; Department of Pharmaceutics, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
authors.forename: Gert
authors.initials: G
authors.lastname: Storm
authors.affiliation: Department of Surgery, YLL School of Medicine, National University of Singapore, Singapore; Cardiovascular Research Institute (CVRI), National University Heart Centre Singapore (NUHCS) and National University Health System (NUHS), 117599, Singapore. Electronic address: surwang@nus.edu.sg.
authors.forename: Jiong-Wei
authors.initials: JW
authors.lastname: Wang
authors.affiliation: Clinical Chemistry and Haematology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Electronic address: r.schiffelers@umcutrecht.nl.
authors.forename: Raymond M
authors.initials: RM
authors.lastname: Schiffelers
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001599:Berberine / Q000008:administration & dosage* / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D015850:Interleukin-6 / Q000032:analysis; D008081:Liposomes; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D000067996:RAW 264.7 Cells; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D002316:Cardiotonic Agents; D015850:Interleukin-6; D008081:Liposomes; D001599:Berberine
keywords: Berberine; Berberine chloride (PubChem CID: 12456); Cardiac function; Inflammation; Liposomes; Myocardial infarction