Microfluidic Directed Self-Assembly of Liposome-Hydrogel Hybrid Nanoparticles
Microfluidic Directed Self-Assembly of Liposome-Hydrogel Hybrid Nanoparticles
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DOI：
10.1021/la100879p
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发表时间：
2010-07-06
期刊：
影响因子：
3.9
通讯作者：
Gaitan, Michael
中科院分区：
文献类型：
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作者：
Hong, Jennifer S.;Stavis, Samuel M.;Gaitan, Michael
我们提出了一种微流控方法来指导温度敏感的脂质体-水凝胶杂化纳米粒子的自组装。我们的方法产生的纳米颗粒的结构特性和高度单分散的大小分布精确控制在一个广泛的范围内相关的靶向输送和控制释放的封装治疗剂。我们使用微流体流体动力学聚焦来控制两种可混溶的纳米颗粒前体溶液（DPPC：胆固醇：DCP磷脂在异丙醇中的制剂和可光聚合的N-异丙基丙烯酰胺在水性巴特勒中的混合物）的对流扩散混合，以形成具有包封的水凝胶前体的纳米级脂质囊泡。这些前体纳米颗粒在芯片外收集，并用紫外（UV）光整体照射以将纳米颗粒内部包裹成水凝胶核。使用多角度激光散射结合不对称流场流分级来表征纳米颗粒尺寸分布，其跨越由微流体混合条件控制的约150至约300 nm直径范围，具有约3%至约5%（相对标准偏差）的多分散性。然后使用透射电子显微镜来确认混合纳米颗粒的球形形状和核-壳组合物。该方法可以扩展到具有工程尺寸/结构-功能关系的其他类似交联混合纳米颗粒系统的定向自组装，用于医疗保健和生命科学应用中的实际使用。
We present a microfluidic method to direct the self-assembly of temperature-sensitive liposome-hydrogel hybrid nanoparticles. Our approach yields nanoparticles with structural properties and highly monodisperse size distributions precisely controlled across a broad range relevant to the targeted delivery and controlled release of encapsulated therapeutic agents. We used microfluidic hydrodynamic focusing to control the convective-diffusive mixing of two miscible nanoparticle precursor solutions (a DPPC:cholesterol:DCP phospholipid formulation in isopropanol and a photopolymerizable N-isopropylacrylamide mixture in aqueous butler) to form nanoscale lipid vesicles with encapsulated hydrogel precursors. These precursor nanoparticles were collected off-chip and were irradiated with ultraviolet (UV) light in bulk to polymerize the nanoparticle interiors into hydrogel cores. Multiangle laser light scattering in conjunction with asymmetric flow field-flow fractionation was used to characterize nanoparticle size distributions, which spanned the approximate to 150 to approximate to 300 nm diameter range as controlled by microfluidic mixing conditions, with a polydispersity of approximate to 3% to approximate to 5% (relative standard deviation). Transmission electron microscopy was then used to confirm the spherical shape and core-shell composition of the hybrid nanoparticles. This method may be extended to the directed self-assembly of other similar cross-linked hybrid nanoparticle systems with engineered size/structure-function relationships for practical use in healthcare and life science applications.