SPIN: rapid synthesis, purification, and concentration of small drug-loaded liposomes

SPIN: rapid synthesis, purification, and concentration of small drug-loaded liposomes
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SPIN:小载药脂质体的快速合成、纯化和浓缩

DOI:
10.1080/08982104.2017.1381115
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发表时间:
2017
影响因子:
4.4
通讯作者:
Agrawal, Nitin
Agrawal, Nitin
中科院分区:
医学2区
文献类型:
--
作者:
Roberts, Steven A.;Parikh, Neil;Blower, Ryan J.;Agrawal, Nitin

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脂质体是研究最多的纳米递送系统之一。然而,只有少数配方获得了FDA的批准。现有的脂质体合成技术是复杂的和专门的,在设计、实施和大规模生产作为治疗剂的脂质体递送系统方面构成主要障碍。在这里,我们展示了一种独特的“可注射纳米载体的合成和纯化”(SPIN)技术,用于使用普通台式设备快速有效地生产小型载药脂质体。合成了平均粒径为80 nm,多分散性为0.13的单层脂质体,无需任何二次后处理技术。证明了代表小分子和大分子药物制剂的葡聚糖(300- 20,000 Da)的包封不影响脂质体特性。99.9%的未包封的分子使用一种新的过滤离心技术,在很大程度上消除了繁琐的超离心方案的需要。最后,通过包封荧光细胞追踪器(CMFDA)并观察脂质体释放和随后转移性乳腺癌细胞(MDA-MB-231)对染料的摄取来验证负载脂质体作为药物递送载体的功能功效。拟议的简化技术解决了现有的挑战与脂质体制备在资源有限的设置,并提供了巨大的潜力,在转化药物开发的进展。
Liposomes are one of the most studied nano-delivery systems. However, only a handful of formulations have received FDA approval. Existing liposome synthesis techniques are complex and specialized, posing a major impediment in design, implementation, and mass production of liposome delivery systems as therapeutic agents. Here, we demonstrate a unique ‘synthesis and purification of injectable nanocarriers’ (SPIN) technology for rapid and efficient production of small drug-loaded liposomes using common benchtop equipment. Unilamellar liposomes with mean diameter of 80 nm and polydispersity of 0.13 were synthesized without any secondary post-processing techniques. Encapsulation of dextrans (300–20,000 Da) representing small and large molecular drug formulations was demonstrated without affecting the liposome characteristics. 99.9% of the non-encapsulated molecules were removed using a novel filter centrifugation technique, largely eliminating the need for tedious ultracentrifugation protocols. Finally, the functional efficacy of loaded liposomes as drug delivery vehicles was validated by encapsulating a fluorescent cell tracker (CMFDA) and observing the liposomal release and subsequent uptake of dye by metastatic breast cancer cells (MDA-MB-231)in vitro. The proposed simplified technique addresses the existing challenges associated with liposome preparation in resource limited settings and offers significant potential for advances in translational pharmaceutical development.
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