Academic Centre for the Biotechnology of Lipid Aggregates, Przybyszewskiego 63/77, 51-148 Wroclaw, Poland.
J Control Release. 2010 Aug 17;146(1):68-75. doi: 10.1016/j.jconrel.2010.05.021. Epub 2010 May 24.
The purpose of this study was to design a new stable liposomal formulation for the anticancer drug idarubicin. Idarubicin is a relatively hydrophobic member of the anthracycline family. It exhibits pronounced bilayer interactions leading to rapid in vivo drug release from liposomes. This rapid drug leakage is due to the presence of cholesterol and charged lipids in the liposomal bilayer. Therefore, a novel method of remote drug loading was developed to prevent rapid drug release from PEGylated cholesterol-containing liposomes. This method uses EDTA disodium or diammonium salt as an agent to form low solubility complexes between the drug and EDTA molecules inside the liposomes, thus yielding improved drug retention. The efficiency of idarubicin encapsulation is close to 98% at a drug to lipid molar ratio of 1:5. An in vitro long-term storage experiment confirmed the high stability of the liposomes. The in vivo studies also showed the superiority of the new idarubicin formulation over the recently used remote loading methods. The plasma level of idarubicin was much higher when EDTA liposomes were used. The presented results fully demonstrate the superiority of the proposed method of idarubicin encapsulation over existing methods. The method offers the possibility of encapsulating not only all the anthracyclines, but also other weakly amphiphilic bases within the liposomes.
本研究旨在设计一种新的稳定的脂质体制剂，用于抗癌药物伊达比星。伊达比星是蒽环类药物家族中相对疏水的成员。它表现出明显的双层相互作用，导致脂质体中的药物迅速从脂质体中释放出来。这种快速的药物泄漏是由于脂质体双层中存在胆固醇和带电荷的脂质。因此，开发了一种新的远程药物加载方法，以防止聚乙二醇化含胆固醇的脂质体中药物的快速释放。该方法使用 EDTA 二钠盐或二铵盐作为一种试剂，在脂质体内形成药物与 EDTA 分子之间的低溶解度络合物，从而提高药物保留率。当药物与脂质的摩尔比为 1:5 时，伊达比星的包封效率接近 98%。体外长期储存实验证实了脂质体的高稳定性。体内研究也表明，新的伊达比星制剂优于最近使用的远程加载方法。当使用 EDTA 脂质体时，伊达比星的血浆水平要高得多。所呈现的结果充分证明了所提出的伊达比星包封方法优于现有方法。该方法不仅提供了将所有蒽环类药物，而且还可以将其他弱两亲性碱基包封在脂质体中的可能性。
