Wang Xinghui, Wang Qiong, Liu Zhihui, Zheng Xiao
Department of Pharmacy, Nanjing University of Chinese Medicine Affiliated Hospital, Nanjing, China.
School of Pharmacy, China Pharmaceutical University, Nanjing, China.
J Pharm Pharmacol. 2017 Jun;69(6):625-632. doi: 10.1111/jphp.12692. Epub 2017 Mar 15.
Berberine (BBR) has shown promising antitumour effects in vitro. However, intravenous administration of BBR solution is complicated by lethal adverse cardiovascular effects. The aim of this study was to prepare common and polyethylene glycol (PEG)-modified long-circulating BBR liposomes and evaluate their efficacy and safety as potential antitumour agents.
Physiochemical properties of common and long-circulating BBR liposomes were characterized including particle size, Zeta potential and thermal stability. Pharmacokinetic and tissue distribution study of liposomal BBR was performed in rats and tumour-bearing nude mice, respectively. Antitumour efficacy and safety were observed in SGC-7901 tumour-xenografted mice.
Berberine liposomes showed homogenous morphology, storage stability and sustained-releasing behaviour in vitro. BBR liposomes led to significantly increased circulation retention of BBR in comparison with BBR solution. In tumour-bearing mice, BBR liposomes selectively increased BBR concentrations in the liver, spleen, lung and tumour, while conferred lower distribution to the heart and kidney. Importantly, chronic administration of BBR liposomes proved effective and safe in suppressing the tumour growth in nude mice, especially the PEG-modified long-circulating liposomes.
Our study suggested that BBR liposomes may provide a safe form of intravenous drug therapy for strengthening the antitumour effects of BBR.
黄连素（BBR）在体外已显示出有前景的抗肿瘤作用。然而，静脉注射BBR溶液会出现致命的不良心血管效应。本研究的目的是制备普通的和聚乙二醇（PEG）修饰的长循环BBR脂质体，并评估它们作为潜在抗肿瘤药物的疗效和安全性。
对普通的和长循环BBR脂质体的理化性质进行表征，包括粒径、Zeta电位和热稳定性。分别在大鼠和荷瘤裸鼠中进行脂质体BBR的药代动力学和组织分布研究。在SGC-7901荷瘤小鼠中观察抗肿瘤疗效和安全性。
黄连素脂质体在体外呈现出均匀的形态、储存稳定性和缓释行为。与BBR溶液相比，BBR脂质体导致BBR的循环保留显著增加。在荷瘤小鼠中，BBR脂质体选择性地增加了肝脏、脾脏、肺和肿瘤中BBR的浓度，而在心脏和肾脏中的分布较低。重要的是，长期给药BBR脂质体在抑制裸鼠肿瘤生长方面被证明是有效和安全的，尤其是PEG修饰的长循环脂质体。
我们的研究表明，BBR脂质体可能为增强BBR的抗肿瘤作用提供一种安全的静脉给药治疗形式。
