以疏水性Fe₃O₄纳米粒子为基的脂质体的制备及表

Preparation and Characterization of Liposomes Embedded with Hydrophobic Fe₃O₄ Nano-Particles

摘要: 磁性脂质体既有脂质体良好生物相容性的优势又具有磁性质而被广泛地用于肿瘤组织的MR增强造影，以实现对肿瘤的预防和早期诊断。本文运用经典的薄膜分散法制备出了一种结构较为新颖的磁性脂质体即负载疏水性Fe₃O₄纳米粒子的脂质体。研究了脂浓度、卵磷脂和胆固醇质量比等因素对磁性脂质体的性能影响，并通过TEM、DLS等手段进行形貌和粒径表征。另外，我们采用邻菲罗啉分光光度法测定Fe含量，以包封率为指标，对影响制备HMLs的因素进行正交实验。结果表明：当脂质体的浓度维持在0.5~2.0 mg/mL，卵磷脂和胆固醇的质量比在2:1~6:1之间时，所得脂质体复合体的稳定性良好，形貌及大小分布均匀，主要呈现夹心式形貌，粒径为125.3 ± 12.9 nm；当初始铁浓度为0.5~3.0 mg/mL时，HMLs的包封率为90%~71.0%。并且HMLs拥有很高的铁含量，这表明其作可潜在的用作肿瘤磁共振成像(MRI)造影剂以增强肿瘤造影的效果。

Abstract: Magnetic liposomes not only have good biocompatibility but also have excellent magnetic proper-ties, so it is widely used in tumor tissue to enhance MR angiography in order to achieve prevention and early diagnosis of tumors. Here, we describe synthesis of magnetic nano-composite liposomes (HMLs) by a thin film dispersing method, based on hydrophobic magnetite (Fe₃O₄) nanoparticles. We studied the effect of lipid concentration, lecithin and cholesterol mass ratio for the properties of HMLs. The results showed that the size of the HMLs containing Fe3O4-OA NPs mainly in a sand-wich-structure is 125.3 ± 12.9 nm obtained by transmission electron microscopy (TEM) and dy-namic light scattering (DLS). The optimized prescription of HMLs has been obtained by orthogonal tests in which encapsulation efficiency of Fe is used as index and phenanthroline absorption spec-trophotometry is used to determine Fe content. The results showed that the best prescription pre- paration process of HMLs is: 0.5 - 2.0 mg/mL of lecithin, and [lecithin]:[cholesterol] = 2:1 - 6:1 (w/w). And while the initial Fe concentration in the solution varied from 0.25 to 3.0 mg/mL, an effective Fe3O4 NPs loading was achieved, with encapsulation efficiency (EE%) from 91.0% to 71.0%. In a word, the results affirm the HMLs possess high Fe concent and can be potentially used to enhance Magnetic Resonance Imaging (MRI) in tumor tissues.