Many promising pharmaceutically active compounds have low solubility in aqueous environments and their encapsulation into efficient drug delivery vehicles is crucial to increase their bioavailability. Lipodisq nanoparticles are approximately 10 nm in diameter and consist of a circular phospholipid bilayer, stabilized by an annulus of SMA (a hydrolysed copolymer of styrene and maleic anhydride). SMA is used extensively in structural biology to extract and stabilize integral membrane proteins for biophysical studies. Here, we assess the potential of these nanoparticles as drug delivery vehicles, determining their cytotoxicity and the in vivo excretion pathways of their polymer and lipid components. Doxorubicin-loaded Lipodisqs were cytotoxic across a panel of cancer cell lines, whereas nanoparticles without the drug had no effect on cell proliferation. Intracellular doxorubicin release from Lipodisqs in HeLa cells occurred in the low-pH environment of the endolysosomal system, consistent with the breakdown of the discoidal structure as the carboxylate groups of the SMA polymer become protonated. Biodistribution studies in mice showed that, unlike other nanoparticles injected intravenously, most of the Lipodisq components were recovered in the colon, consistent with rapid uptake by hepatocytes and excretion into bile. These data suggest that Lipodisqs have the potential to act as delivery vehicles for drugs and contrast agents.

中文翻译：

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盘状，基于脂质的药物递送载体：含有阿霉素的Lipodisq纳米颗粒的理化特性，毒性和体内生物分布研究。

许多有前途的药物活性化合物在水性环境中的溶解度较低，并且将其封装到有效的药物传递载体中对于提高其生物利用度至关重要。Lipodisq纳米颗粒的直径约为10 nm，由圆形磷脂双层构成，该双层双层由SMA环（苯乙烯和马来酸酐的水解共聚物）稳定。SMA在结构生物学中被广泛使用，以提取和稳定完整的膜蛋白，用于生物物理研究。在这里，我们评估了这些纳米颗粒作为药物传递载体的潜力，确定了它们的细胞毒性和体内它们的聚合物和脂质成分的排泄途径。装载阿霉素的Lipodisqs在一组癌细胞系中具有细胞毒性，而没有药物的纳米颗粒对细胞增殖没有影响。HeLa细胞中Lipodisqs释放的细胞内阿霉素发生在溶酶体系统的低pH环境中，这与SMA聚合物的羧基化为质子化时盘状结构的破坏一致。在小鼠中进行的生物分布研究表明，与其他静脉内注射的纳米颗粒不同，大多数Lipodisq组分在结肠中被回收，这与肝细胞的快速摄取和排泄到胆汁中是一致的。这些数据表明，Lipodisqs有潜力充当药物和造影剂的传递载体。