Validation of the reconstituted high-density lipoprotein (rHDL) drug delivery platform using dilauryl fluorescein (DLF)
Validation of the reconstituted high-density lipoprotein (rHDL) drug delivery platform using dilauryl fluorescein (DLF)
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DOI：
10.1007/s13346-010-0012-0
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发表时间：
2011-04-01
影响因子：
5.4
通讯作者：
Lacko, Andras G.
中科院分区：
文献类型：
--
作者：
McConathy, Walter J.;Paranjape, Sulabha;Lacko, Andras G.
双月桂酰荧光素（DLF）是一种脂溶性分子，当月桂酸被水解除去时，它会发出荧光。这些研究的目的是评价DLF作为重组高密度脂蛋白（rHDL）作为疏水药物转运载体的功能的潜在探针。含有DLF的rHDL纳米颗粒的特征在于它们的物理/化学性质，包括分子直径、分子量、化学组成和浮力密度。我们研究了过表达清道夫受体（SR-B1）的细胞从rHDL中摄取DLF的情况，已知清道夫受体可促进细胞从HDL中选择性摄取胆固醇酯。这些研究表明，DLF可以被纳入rHDL和重新分布在血浆室。此外，这些研究表明，过表达SR-B1受体的细胞对rHDL中DLF的摄取和水解增强，表明受体介导的机制参与其中。基于与人血浆孵育期间与游离DLF相比rHDL/ DLF水解速率较低，DLF掺入rHDL纳米颗粒似乎可防止体循环中的水解。因此，DLF可以用作探针来跟踪HDL核心成分（包括癌症化疗剂）的运动和代谢。
Dilauryl fluorescein (DLF) is a lipid soluble molecule that becomes fluorescent when lauric acid is removed by hydrolysis The purpose of these studies was to evaluate DLF as a potential probe for the function of reconstituted high-density lipoproteins (rHDL) as hydrophobic drug transport vehicles. The DLF containing rHDL nanoparticles were characterized regarding their physical/chemical properties, including molecular diameter, molecular weight, chemical composition, and buoyant density. We investigated the uptake of DLF from rHDL in cells that overexpress the scavenger receptor (SR-B1), known to facilitate the selective cellular uptake of cholesteryl esters from HDL. These studies show that DLF can be incorporated into rHDL and redistributed in the plasma compartment. In addition, these studies demonstrated an enhanced uptake and hydrolysis of DLF from rHDL by cells that overexpress the SR-B1 receptor, suggesting the involvement of a receptor mediated mechanism. The incorporation of DLF into the rHDL nanoparticles appear to protect against hydrolysis in the systemic circulation based on the lower rate of rHDL/ DLF hydrolysis compared with the free DLF during incubation with human plasma. DLF may thus be used as a probe to track the movement and metabolism of HDL core constituents, including cancer chemotherapeutic agents.