Liposome encapsulated berberine treatment attenuates cardiac dysfunction after myocardial infarction

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• 作者：Iris E. Allijn^a ; ¹ ; Bertrand M.S. Czarny^b ; ^c ; ¹ ; Xiaoyuan Wang^d ; ^e ; Suet Yen Chong^d ; ^e ; Marek Weiler^f ; Acarilia Eduardo da Silva^a ; ² ; Josbert M. Metselaar^a ; ^f ; Carolyn Su Ping Lam^g ; ^h ; Giorgia Pastorin^b ; Dominique P.V. de Kleijn^d ; ⁱ ; ^j ; Gert Storm^a ; ^c ; Jiong-Wei Wang^d ; ^e ; ^{surwang@nus.edu.sg} ; Raymond M. Schiffelers^k ; ^{r.schiffelers@umcutrecht.nl}
• 关键词：BB ; berberine chloride ; BB-lip ; berberine liposomes ; CAD ; charged aerosol detector ; CHF ; congestive heart failure ; DLS ; dynamic light scattering ; HBS ; HEPES buffered saline ; HF ; heart failures ; LPS ; lipopolysaccharide ; LVEF ; left ventricular ejection fraction ; MI ; myocardial infarction ; PBS ; phosphate buffered saline ; RT ; room temperature
• 刊名：Journal of Controlled Release
• 出版年：2017
• 出版时间：10 February 2017
• 年：2017
• 卷：247
• 期：Complete
• 页码：127-133
• 全文大小：998 K
• 卷排序：247

文摘

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.