Liposome encapsulated berberine treatment attenuates cardiac dysfunction after myocardial infarction.

Autor: Allijn IE; Department of Biomaterials Science and Technology, University of Twente, Enschede, Drienerlolaan 5, 7522 NB Enschede, The Netherlands., Czarny BMS; Department of Pharmacy, National University of Singapore, Science Drive 2, 117543, Singapore; Department of Pharmaceutics, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands., Wang X; 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., Chong SY; 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., Weiler M; Department of Experimental Molecular Imaging, University Clinic RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany., da Silva AE; Department of Biomaterials Science and Technology, University of Twente, Enschede, Drienerlolaan 5, 7522 NB Enschede, The Netherlands., Metselaar JM; 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., Lam CSP; 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., Pastorin G; Department of Pharmacy, National University of Singapore, Science Drive 2, 117543, Singapore., de Kleijn DPV; 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., Storm G; 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., Wang JW; 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., Schiffelers RM; Clinical Chemistry and Haematology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Electronic address: r.schiffelers@umcutrecht.nl.
Jazyk: angličtina
Zdroj: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2017 Feb 10; Vol. 247, pp. 127-133. Date of Electronic Publication: 2017 Jan 05.
DOI: 10.1016/j.jconrel.2016.12.042
Abstrakt: 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 (IC 50 =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.
(Copyright © 2017 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE