基于微流控技术的纳米药物可控组装
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摘要
本研究主要报道基于微流控的载药杂化纳米颗粒的合成。由于微流控管道中具有高效的流体混合与精确的流体控制,基于微流控的纳米颗粒合成方法现相对于常规方法而言更加有利于产生出结构可控的纳米颗粒。最近,我们利用一种两级微流控芯片,一步合成了PLGA作为核心,磷脂作为外壳的杂化纳米颗粒。通过调节磷脂层结构与磷脂聚合物之间的水腔,我们实现了对于纳米颗粒硬度的调控。进一步的研究表明,较硬的纳米颗粒具有较高的细胞摄取能力与药物递送能力。~([1]),~([2])同时,我们发现改变管道中流体的总流速可以调节所获得的纳米颗粒的尺寸。高流速条件下,该微流控芯片可以合成出尺寸较小,粒径分布更为均一的纳米颗粒。~([3])除此之外,我们还开发了一种三级微流控芯片。利用这种三级芯片,我们构建出具有空心结构的胶囊型杂化纳米颗粒。该胶囊型纳米颗粒可以用于多种亲水性物质的高效包载与体内外递送。~([4])
Microfluidic based controlled hybrid nanoparticle synthesizing methods have been developed. The rapid mixing and precise control of fluids in the microfluidic chip are helpful to generate nanoparticles with controlled structure. Recently, a two-stage microfluidic platform is designed for synthesizing PLGA-core lipid-shell nanoparticles in a single-step fabrication and tunes the particle rigidity by varying the amount of internal water. With this platform, we found that cellular and in vivo uptake of hybrid nanoparticles is governed by the particle rigidity. Moreover, we can manipulate the size of the nanoparticles by changing the flow rate during synthesizing. In addition, we also present a hollow-structured rigid nanovesicle(RNV) fabricated by a multi-stage microfluidic chip in one step, to effectively entrap various hydrophilic reagents inside. The RNV contains a hollow water core, a rigid PLGA shell, and an outermost lipid layer. The RNV can be used to encapsulate hydrophilic reagents with high loading efficiency.
引文
[1]Sun J.,Zhang L.,Wang J.,Feng Q.,Liu D.,Yin Q.,Xu D.,Wei Y.,Ding B.,Shi X.and Jiang X.,Adv.Mater.,2015,27:1402.
    [2]Zhang L.,Feng Q.,Wang J.,Zhang S.,Ding B.,Wei Y.,Dong M.,Ryu J.Y.,Yoon T.Y.,Shi X.,Sun J.and Jiang X.,ACS Nano,2015,9:9912.
    [3]Feng Q.,Zhang L.,Liu C.,Li X.,Hu G.,Sun J.and Jiang X.,Biomicrofluidics,2015,9:052604.
    [4]Zhang L.,Feng Q.,Wang J.,Sun J.,Shi X.and Jiang X.,Angew.Chem.,Int.Ed.,2015,54:3952.

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