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Abstract：
The present study investigates the possible use of manganese (Mn)-based liposomal formulations for diagnostic applications in imaging techniques such as magnetic resonance imaging (MRI), with the aim of overcoming the toxicity limitations associated with the use of free Mn2+. Specifically, anionic liposomes carrying two model Mn(II)-based compounds, MnCl2 (MC) and Mn(HMTA) (MH), were prepared and characterised in terms of morphology, size, loading capacity, and in vitro activity. Homogeneous dispersions characterised mainly by unilamellar vesicles were obtained; furthermore, no differences in size and morphology were detected between unloaded and Mn-loaded vesicles. The encapsulation efficiency of MC and MH was evaluated on extruded liposomes by means of ICP-OES analysis. The obtained results showed that both MC and MH are almost completely retained by the lipid portion of liposomes (LPs), with encapsulation efficiencies of 99.7% for MC and 98.8% for MH. The magnetic imaging properties of the produced liposomal formulations were investigated for application in a potential preclinical scenario by collecting magnetic resonance images of a phantom designed to compare the paramagnetic contrast properties of free MC and MH compounds and the corresponding manganese-containing liposome dispersions. It was found that both LP-MC and LP-MH at low concentrations (0.5 mM) show better contrast (contrast-to-noise ratios of 194 and 209, respectively) than solutions containing free Mn at the same concentrations (117 and 134, respectively) and are safe to use on human cells at the selected dose. Taken together, the results of this comparative analysis suggest that these liposome-containing Mn compounds might be suitable for diagnostic purposes.
摘要：
本研究调查了基于锰（Mn）的脂质体制剂在磁共振成像（MRI）等成像技术中的诊断应用的可能用途。目的是克服与使用游离Mn2+相关的毒性限制。具体来说,阴离子脂质体携带两种基于Mn(II)的模型化合物，MnCl2（MC）和Mn（HMTA）（MH），在形态方面进行了准备和表征，尺寸,装载能力,和体外活性。获得了主要以单层囊泡为特征的均相分散体；此外，在未负载和负载锰的囊泡之间没有检测到大小和形态的差异。通过ICP-OES分析在挤出的脂质体上评估MC和MH的包封效率。获得的结果表明，MC和MH几乎完全被脂质体（LPs）的脂质部分保留，MC的封装效率为99.7%，MH的封装效率为98.8%。通过收集设计用于比较游离MC和MH化合物与相应的含锰脂质体分散体的顺磁对比特性的体模的磁共振图像,研究了所生产的脂质体制剂的磁成像特性,用于在潜在的临床前情况中的应用。发现低浓度(0.5mM)的LP-MC和LP-MH显示出比含有相同浓度的游离Mn的溶液(分别为117和134)更好的对比度(对比噪声比分别为194和209),并且在选定剂量下用于人细胞是安全的。一起来看,比较分析的结果表明,这些含脂质体的Mn化合物可能适用于诊断目的。
