Liposome encapsulated berberine treatment attenuates cardiac dysfunction after myocardial infarction

Inflammation is a known mediator of adverse ventricular remodeling aftermyocardial infarction (MI) thatmay lead to reduction of ejection fraction and subsequent heart failure. Berberine is a isoquinoline quarternary alka- loid from plants that has been associated with anti-inflammatory, anti-oxidative, and cardioprotective proper- ties. 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 func- tion againstMI in vivo. Berberine-loaded liposomeswere prepared by ethanol injection and characterized. They contained 0.3mg/mL of the drug andwere 0.11 μmin diameter. Subsequently theywere tested for IL-6 secretion inhibition in RAW264.7macrophages and for cardiac function protection against adverse remodeling afterMI in C57BL/6J mice. In vitro, free berberine significantly inhibited IL-6 secretion (IC50=10.4 μM), whereas encapsu- lated 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 afterMI by 64% as compared to control liposomes and free berberine. In conclusion, liposomal encapsulation enhanced the solu- bility of berberine in buffer and preserves ejection fraction afterMI. This shows that delivery of berberine-loaded liposomes significantly improves its therapeutic availability and identifies berberine-loaded liposomes as poten- tial treatment of adverse remodeling after MI.