Berberine-loaded liposomes for oral delivery: Preparation, physicochemical characterization and in-vivo evaluation in an endogenous hyperlipidemic animal model

Berberine (BBR) is a plant-origin quaternary isoquinoline alkaloid presenting exogenous cholesterol lowering and anti-hyperlipidemia therapeutic effects. The aim of this study was to design and generate BBR-loaded proliposomes (PLs) as solid templates for high-dose liposomes and consequently, to enhance the oral bioavailability and therapeutic effect of BBR. An air-suspension coating (layering) method was used for generating BBR-loaded PLs. The size, distribution size, morphology, and entrapment efficiency (EE) of the final reconstituted liposomes were assessed. The oral bioavailability and endogenous cholesterol lowering effects of BBR loaded in liposomes were investigated in rats and mice, respectively. The BBR-loaded PLs showed a smooth BBR-embedded film around micron-scale carrier particles (mannitol). The reconstituted BBR-loaded liposomes had a nano-scale average size (116.6 ± 5.8 nm), narrow size distribution (polydispersity index, PDI 0.269 ± 0.038), and high EE (87.8 ± 1.0%). The oral bioavailability of reconstituted BBR-loaded liposomes at a dose of 100 mg/kg in rats was increased even 628% compared to that obtained with pure BBR (according to 90% confidence interval). The BBR-loaded liposomes at the daily oral dose 100 mg/kg in P-407- reduced total cholesterol, triglycerides and low-density lipoprotein cholesterol (LDL-C) in hyperlipidemic mice by 15.8%, 38.2%, and 57.0%, respectively.