Microfluidic-Generated Immunomodulatory Nanoparticles and Formulation-Dependent Effects on Lipopolysaccharide-Induced Macrophage Inflammation.
Microfluidic-Generated Immunomodulatory Nanoparticles and Formulation-Dependent Effects on Lipopolysaccharide-Induced Macrophage Inflammation.
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微流体产生的免疫调节纳米颗粒和对脂多糖诱导的巨噬细胞炎症的制剂依赖性作用。
DOI：
10.1208/s12248-021-00645-2
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发表时间：
2021-12-02
期刊：
影响因子：
--
通讯作者：
Pearson RM
中科院分区：
文献类型：
--
作者：
Truong N;Black SK;Shaw J;Scotland BL;Pearson RM
纳米颗粒（NPs）已经成为用于巨大治疗有效载荷的高度有用和临床可转化的药物递送平台。通过精确调节其物理化学性质，NP可以被工程化以表现出受控的药物释放性质、增强的循环时间、改善的细胞摄取和靶向以及降低的毒性特征。用于生产聚合物NP的常规批量方法受到控制其尺寸和多分散性的能力、批次间可变性、显著的制备时间和低回收率的影响。在这里，我们描述了一种高通量微流体方法的开发和优化，以产生无载物的免疫调节纳米颗粒（iNP）及其制剂依赖性抗炎特性，用于调节脂多糖（LPS）诱导的巨噬细胞反应。使用聚乳酸（PLA）作为核心形成聚合物，开发和优化了一种快速和可调的微流体流体动力学流动聚焦方法，以系统地评估聚合物和表面活性剂浓度，表面活性剂化学和流速比（FRR）对iNP形成的作用。然后制备一组具有6种不同表面化学和2种FRR的iNP，以使用用Toll样受体（TLR）4激动剂LPS刺激的骨髓来源的巨噬细胞来评估其固有的抗炎作用。最后，使用各种冷冻保护剂和组合进行冻干研究，以确定iNP储存的优选条件。总的来说，我们证明了一种高度受控和可重复的方法，用于使用微流体配制iNP及其制剂依赖性固有的抗炎免疫调节特性，这代表了一种潜在的有希望的炎症管理策略。
Nanoparticles (NPs) have emerged as a highly useful and clinically translatable drug delivery platform for vast therapeutic payloads. Through the precise tuning of their physicochemical properties, NPs can be engineered to exhibit controlled drug release properties, enhanced circulation times, improved cellular uptake and targeting, and reduced toxicity profiles. Conventional bulk methods for the production of polymeric NPs suffer from the ability to control their size and polydispersity, batch-to-batch variability, significant preparation times, and low recovery. Here, we describe the development and optimization of a high-throughput microfluidic method to produce cargo-less immunomodulatory nanoparticles (iNPs) and their formulation-dependent anti-inflammatory properties for the modulation of lipopolysaccharide (LPS)-induced macrophage responses. Using poly(lactic acid) (PLA) as the core-forming polymer, a rapid and tunable microfluidic hydrodynamic flow focusing method was developed and optimized to systematically evaluate the role of polymer and surfactant concentration, surfactant chemistry, and flow rate ratio (FRR) on the formation of iNPs. A set of iNPs with 6 different surface chemistries and 2 FRRs was then prepared to evaluate their inherent anti-inflammatory effects using bone marrow-derived macrophages stimulated with the Toll-like receptor (TLR) 4 agonist, LPS. Finally, a lyophilization study was performed using various cryoprotectants and combinations to identify preferable conditions for iNP storage. Overall, we demonstrate a highly controlled and reproducible method for the formulation of iNPs using microfluidics and their formulation-dependent inherent anti-inflammatory immunomodulatory properties, which represents a potentially promising strategy for the management of inflammation.
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