The roadmap to micro: Generation of micron-sized polymeric particles using a commercial microfluidic system.
The roadmap to micro: Generation of micron-sized polymeric particles using a commercial microfluidic system.
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DOI：
10.1002/jbm.a.37358
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发表时间：
2022-05
期刊：
影响因子：
--
通讯作者：
Lewis JS
中科院分区：
文献类型：
--
作者：
Cruz-Acuña M;Kakwere H;Lewis JS
微流体辅助的颗粒制造提供了一种途径来规避与聚合物颗粒产生的传统方法相关的缺点，例如低药物负载效率、控制包封的药物释放速率的挑战、颗粒物理性质的批次间差异和制剂不稳定性。然而，这种方法主要产生具有纳米尺寸的颗粒，这限制了药物递送方式。在此，我们系统地研究了使用微流体系统NanoAssemblr工作台生成微米级聚（乳酸-共-乙醇酸）（PLGA）颗粒的参数。最初，我们使用了两种有机溶剂，已报道适用于制造的PLGA纳米粒子-丙酮和乙腈。随后，我们有条不紊地操纵聚合物浓度，有机：水的流速，总流速，有机相组成，和表面活性剂浓度开发的路线，用于制造微米级的PLGA颗粒。此外，我们将羟氯喹（HCQ），一种临床批准的药物，用于疟疾和淋巴瘤，并测量其掺入如何影响颗粒的物理化学性质。简而言之，通过包括乙酸乙酯（极性较小的溶剂）来改变有机相组成，产生微米级颗粒，以及增加的多分散性指数（PDI）。在添加这些溶剂混合物之后调节聚乙烯醇（PVA）的表面活性剂浓度使得大颗粒具有较低的PDI可变性。此外，HCQ的包封以PVA浓度依赖的方式影响颗粒流体动力学直径和PDI。最后，我们证明了未加载和加载HCQ的颗粒不影响RAW 264.7巨噬细胞的活力。这项研究提供了一个路线，用于制造生物相容性，载药，微米级的聚合物颗粒，特别是当感兴趣的药物是不容易溶于传统的有机溶剂。
Microfluidic-assisted particle fabrication provides a route to circumvent the disadvantages associated with traditional methods of polymeric particle generation, such as low drug loading efficiency, challenges in controlling encapsulated drug release rates, batch-to-batch variability in particle physical properties and formulation instability. However, this approach primarily produces particles with nanometer size dimensions, which limits drug delivery modalities. Herein, we systematically studied parameters for the generation of micron-sized poly(lactic-co-glycolic) acid (PLGA) particles using a microfluidic system, the NanoAssemblr benchtop. Initially, we used two organic solvents that have been reported suitable for the fabrication of PLGA nanoparticles - acetone and acetonitrile. Subsequently, we methodically manipulated polymer concentration, organic:aqueous flow rates, total flow rate, organic phase composition, and surfactant concentration to develop a route for the fabrication of micron-sized PLGA particles. Further, we incorporated hydroxychloroquine (HCQ), a clinically approved drug to for malaria and lymphoma, and measured how its incorporation impacted particle physicochemical properties. Briefly, altering the organic phase composition by including ethyl acetate (less polar solvent), resulted in micron-scale particles, as well as increased polydispersity indexes(PDIs). Adjusting the surfactant concentration of poly vinyl alcohol (PVA) after the addition of these solvent mixtures rendered large particles with lower PDI variability. Moreover, encapsulation of HCQ influenced particle hydrodynamic diameter and PDI in a PVA concentration dependent manner. Finally, we demonstrated that unloaded and HCQ-loaded particles did not affect the viability of RAW 264.7 macrophages. This study provides an itinerary for fabricating biocompatible, drug-loaded, micron-sized polymeric particles, particularly when the drug of interest is not readily soluble in conventional organic solvents.
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影响因子：
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作者：
Makadia HK;Siegel SJ
通讯作者：
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DOI：
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发表时间：
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