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首页> 外文期刊>Biotechnology Progress >Controllable Microfluidic Synthesis of Multiphase Drug-Carrying Lipospheres for Site-Targeted Therapy
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Controllable Microfluidic Synthesis of Multiphase Drug-Carrying Lipospheres for Site-Targeted Therapy

机译：可控微流合成多相药物脂质体的定点治疗

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摘要

We report the production of micrometer-sized gas-filled lipospheres using digital (droplet-based) microfluidics technology for chemotherapeutic drug delivery. Advantages of on-chip synthesis include a monodisperse size distribution (polydispersity index (σ) values of <5%) with consistent stability and uniform drug loading. Photolithography techniques are applied to fabricate novel PDMS-based microfluidic devices that feature a combined dual hydrody-namic flow-focusing region and expanding nozzle geometry with a narrow orifice. Spherical vehicles are formed through flow-focusing by the self-assembly of phospholipids to a lipid layer around the gas core,followed by a shear-induced break off at the orifice. The encapsulation of an extra oil layer between the outer lipid shell and inner bubble gaseous core allows the transport of highly hydrophobic and toxic drugs at high concentrations. Doxorubicin (Dox) entrapment is estimated at 15 mg mL~(-1) of particles packed in a single ordered layer. In addition,the attachment of targeting ligands to the lipid shell allows for direct vehicle binding to cancer cells. Preliminary acoustic studies of these monodisperse gas lipospheres reveal a highly uniform echo correlation of greater than 95%. The potential exists for localized drug concentration and release with ultrasound energy.
机译：我们报告了使用数字（基于液滴的）微流控技术进行化学药物递送的微米级充气脂质球的生产。芯片上合成的优势包括具有稳定稳定性和均匀载药量的单分散尺寸分布（多分散指数（σ）值<5％）。光刻技术被应用于制造新颖的基于PDMS的微流控设备，该设备的特征在于结合了两个水力流和双流体流聚焦区域，并通过狭窄的孔口扩大了喷嘴的几何形状。球形载体是通过使磷脂自组装到气体核心周围的脂质层上，然后在孔口处发生剪切诱导的断裂而通过流动聚集而形成的。在外部脂质壳和内部气泡气态核之间的额外油层的包封允许以高浓度运输高度疏水和有毒的药物。阿霉素（Dox）截留量估计为15 mg mL〜（-1）颗粒，堆积在一个有序层中。另外，靶向配体与脂质壳的连接允许直接将载体结合至癌细胞。对这些单分散性气体脂球的初步声学研究表明，回声相关性非常均匀，大于95％。存在局部药物集中和通过超声能量释放的潜力。

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