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用于生物医学应用的纳米颗粒的微流体制备。

Microfluidic formulation of nanoparticles for biomedical applications.

机构信息

Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, 19104, USA.

Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, 19104, USA; Department of Electrical and Systems Engineering, University of Pennsylvania, Philadelphia, PA, 19104, USA; Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA, 19104, USA.

出版信息

Biomaterials. 2021 Jul;274:120826. doi: 10.1016/j.biomaterials.2021.120826. Epub 2021 Apr 26.

Abstract

Nanomedicine has made significant advances in clinical applications since the late-20th century, in part due to its distinct advantages in biocompatibility, potency, and novel therapeutic applications. Many nanoparticle (NP) therapies have been approved for clinical use, including as imaging agents or as platforms for drug delivery and gene therapy. However, there are remaining challenges that hinder translation, such as non-scalable production methods and the inefficiency of current NP formulations in delivering their cargo to their target. To address challenges with existing formulation methods that have batch-to-batch variability and produce particles with high dispersity, microfluidics-devices that manipulate fluids on a micrometer scale-have demonstrated enormous potential to generate reproducible NP formulations for therapeutic, diagnostic, and preventative applications. Microfluidic-generated NP formulations have been shown to have enhanced properties for biomedical applications by formulating NPs with more controlled physical properties than is possible with bulk techniques-such as size, size distribution, and loading efficiency. In this review, we highlight advances in microfluidic technologies for the formulation of NPs, with an emphasis on lipid-based NPs, polymeric NPs, and inorganic NPs. We provide a summary of microfluidic devices used for NP formulation with their advantages and respective challenges. Additionally, we provide our analysis for future outlooks in the field of NP formulation and microfluidics, with emerging topics of production scale-independent formulations through device parallelization and multi-step reactions within droplets.

摘要

自 20 世纪后期以来,纳米医学在临床应用方面取得了重大进展,部分原因是其在生物相容性、效力和新型治疗应用方面具有独特的优势。许多纳米颗粒 (NP) 疗法已被批准用于临床,包括作为成像剂或作为药物输送和基因治疗的平台。然而,仍然存在一些阻碍转化的挑战,例如非规模化的生产方法和当前 NP 制剂在将其货物递送到目标位置方面的效率低下。为了解决现有制剂方法的挑战,这些方法具有批次间可变性并且产生高分散性的颗粒,微流控设备——在微米尺度上操纵流体的设备——已经显示出巨大的潜力,可以为治疗、诊断和预防应用生成可重复的 NP 制剂。通过使用微流控技术可以将 NP 制成具有更可控的物理性质,这比使用批量技术更有可能实现,例如尺寸、尺寸分布和负载效率,从而显示出对生物医学应用具有增强性能的 NP 制剂。在这篇综述中,我们强调了用于 NP 制剂的微流控技术的进展,重点介绍了基于脂质的 NP、聚合物 NP 和无机 NP。我们提供了用于 NP 制剂的微流控设备的摘要,以及它们的优点和各自的挑战。此外,我们还对 NP 制剂和微流控领域的未来前景进行了分析,提出了通过设备并行化和液滴内多步反应实现生产规模独立制剂的新兴主题。

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