TY - JOUR
T1 - Liposome encapsulated berberine treatment attenuates cardiac dysfunction after myocardial infarction
AU - Allijn, Iris E.
AU - Czarny, Bertrand M S
AU - Wang, Xiaoyuan
AU - Chong, Suet Yen
AU - Weiler, Marek
AU - da Silva, Acarilia Eduardo
AU - Metselaar, Josbert M.
AU - Lam, Carolyn Su Ping
AU - Pastorin, Giorgia
AU - de Kleijn, Dominique P V
AU - Storm, Gert
AU - Wang, Jiong Wei
AU - Schiffelers, Raymond M.
N1 - Funding Information:
This research was funded by NanoNextNL (03D.11, RMS) and the National Medical Research Council CS-IRG grant (13nov024) (CSPL&DPVdK) and the ATTRaCT SPF (13nov002) grant (CSPL&DPVdK).
Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2017/2/10
Y1 - 2017/2/10
N2 - 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 0.3 mg/mL of the drug and were 0.11 μm 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 = 10.4 μM), 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.
AB - 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 0.3 mg/mL of the drug and were 0.11 μm 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 = 10.4 μM), 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.
KW - Berberine
KW - Cardiac function
KW - Inflammation
KW - Liposomes
KW - Myocardial infarction
UR - http://www.scopus.com/inward/record.url?scp=85009090167&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2016.12.042
DO - 10.1016/j.jconrel.2016.12.042
M3 - Article
C2 - 28065862
AN - SCOPUS:85009090167
SN - 0168-3659
VL - 247
SP - 127
EP - 133
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -