Faculty of Pharmacy, Duy Tan University, 03 Quang Trung Street, Da Nang 550000, Viet Nam; Hanoi University of Pharmacy, 13-15 Le Thanh Tong Street, Hoan Kiem District, 110403 Hanoi, Viet Nam; Institute of Pharmacy, Faculty of Medicine, University of Tartu, Nooruse Street 1, 50411 Tartu, Estonia.
Hanoi University of Pharmacy, 13-15 Le Thanh Tong Street, Hoan Kiem District, 110403 Hanoi, Viet Nam.
Int J Pharm. 2022 Mar 25;616:121525. doi: 10.1016/j.ijpharm.2022.121525. Epub 2022 Jan 29.
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.
小檗碱（BBR）是一种植物来源的季铵异喹啉生物碱，具有降低外源性胆固醇和抗高血脂的治疗作用。本研究旨在设计并制备小檗碱载脂质体（PLs）作为高剂量脂质体的固体模板，从而提高小檗碱的口服生物利用度和治疗效果。采用空气悬浮包衣（层积）法制备小檗碱载 PLs。评估最终重建脂质体的粒径、分布粒径、形态和包封效率（EE）。分别在大鼠和小鼠中研究了载于脂质体中的小檗碱的口服生物利用度和内源性降低胆固醇作用。小檗碱载 PLs 显示出微米级载体颗粒（甘露醇）周围的光滑小檗碱嵌入膜。重建的小檗碱载脂质体具有纳米级平均粒径（116.6±5.8nm）、窄粒径分布（多分散指数，PDI 0.269±0.038）和高 EE（87.8±1.0%）。与纯小檗碱相比，以 100mg/kg 剂量口服重建的小檗碱载脂质体在大鼠中的口服生物利用度提高了 628%（根据 90%置信区间）。载小檗碱的脂质体在 100mg/kg 的每日口服剂量下，可使高脂血症小鼠的总胆固醇、甘油三酯和低密度脂蛋白胆固醇（LDL-C）分别降低 15.8%、38.2%和 57.0%。
