Effective-Loading of Platinum-Chloroquine into PEGylated Neutral and Cationic Liposomes as a Drug Delivery System for Resistant Malaria Parasites
Effective-Loading of Platinum-Chloroquine into PEGylated Neutral and Cationic Liposomes as a Drug Delivery System for Resistant Malaria Parasites
复制标题
DOI：
10.1248/bpb.b16-00914
复制
发表时间：
2017-06-01
影响因子：
2
通讯作者：
Ozeki, Tetsuya
中科院分区：
文献类型：
--
作者：
Ibrahim, Shaimaa;Tagami, Tatsuaki;Ozeki, Tetsuya
反式二磷酸氯喹铂（PtCQ）是一种新型抗疟药，用于对抗对传统药物耐药的寄生虫。PtCQ是通过混合铂和二磷酸氯喹（CQ）合成的。本研究探讨了两种有效的方法，形成纳米药物，PtCQ负载的脂质体，作为一个潜在的抗疟药物输送系统：薄药物脂质膜的方法，将药物纳入脂质体膜，和远程加载的方法，将药物加载到内部的阳离子脂质体。因此，膜包含PEG化的中性或阳离子脂质体。使用薄药物脂质膜方法将PtCQ有效地装载到PEG化中性和阳离子脂质体中（包封效率，EE：中性脂质体为76.1 +/- 6.7%，药物与脂质重量比为1：14;阳离子脂质体为70.4 +/- 9.8%，药物与脂质重量比为1：14）。使用远程加载方法比通过薄药物脂质膜方法将更多的PtCQ加载到PEG化中性脂质体中，并且EE最大（中性脂质体为96.1 +/-4.5%，1：7（w/w））。使用远程加载方法将PtCQ包封在包含不同量的阳离子脂质（0-20摩尔%; EE：96.9-92.3%）的PEG化阳离子脂质体中。PEG化的中性脂质体和阳离子脂质体在4 ℃下储存两个月后表现出最小的PtCQ泄漏，并且在37 ℃下体外培养72小时的条件下进一步表现出几乎没有释放。这些结果为设计未来靶向疟原虫的基于脂质体的体内药物递送系统提供了有用的框架。
The trans platinum chloroquine diphosphate dichloride (PtCQ) is a new type of antimalarial drug used to fight parasites resistant to traditional drugs. PtCQ is synthesized by mixing platinum and chloroquine di-phosphate (CQ). This study examines two efficient methods for forming a nanodrug, PtCQ-loaded liposomes, for use as a potential antimalarial drug-delivery system: the thin drug-lipid film method to incorporate the drug into a liposomal membrane, and a remote-loading method to load the drug into the interior of a cationic liposome. The membranes accordingly comprised PEGylated neutral or cationic liposomes. PtCQ was efficiently loaded into PEGylated neutral and cationic liposomes using the thin drug lipid film method (encapsulation efficiency, EE: 76.1 +/- 6.7% for neutral liposomes, 1 :14 drug-to-lipid weight ratio; 70.4 +/- 9.8% for cationic liposomes, 1:14 drug-to-lipid weight ratio). More PtCQ was loaded into PEGylated neutral liposomes using the remote-loading method than by the thin drug lipid film method and the EE was maximum (96.1 +/- 4.5% for neutral liposomes, 1:7 (w/w)). PtCQ was encapsulated in PEGylated cationic liposomes comprising various amounts of cationic lipids (0-20 mol%; EE: 96.9-92.3%) using the remote-loading method. PEGylated neutral liposomes and cationic liposomes exhibited minimum leakage of PtCQ after two months' storage at 4 degrees C, and further exhibited little release under in vitro culture conditions at 37 degrees C for 72 h. These results provide a useful framework for the design of future liposome-based in vivo drug delivery systems targeting the malaria parasite.