Shaw Jacob R, Vaidya Radha, Xu Fanny, Dharmaraj Shruti, Pearson Ryan M
Department of Microbiology and Immunology, University of Maryland School of Medicine 685 W. Baltimore Street Baltimore MD 21201 USA.
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy 20 N. Pine Street Baltimore MD 21201 USA
RSC Pharm. 2024 Nov 26;2(1):135-146. doi: 10.1039/d4pm00233d. eCollection 2025 Jan 21.
Polymeric nanoparticles (NPs) are traditionally formulated using batch methodologies that are poorly scalable and require time consuming, hands-on purification procedures. Here, we prepared poly(lactic acid) (PLA)-based polymeric NPs using a scalable microfluidics-based method and systematically investigated the impact of purification method (centrifugation tangential flow filtration (TFF)) to remove poly(vinyl alcohol) (PVA) on macrophage uptake, anti-inflammatory effects, biodistribution, and protein corona formation. TFF purification demonstrated significantly higher recovery of NPs compared to the centrifugation method, with little-to-no aggregation observed. PVA removal efficiency was superior with centrifugation, although TFF was comparable. NP cellular association, anti-inflammatory activity, and biodistribution studies suggested purification method-dependent alterations, which were correlated with protein corona profiles. This study underscores the potential of TFF, combined with microfluidics, as an efficient and high-yield purification method for NPs, and reveals the need for extensive confirmation of NP biological activity alongside physicochemical properties when developing NP therapeutics at-scale.
传统上，聚合物纳米颗粒（NPs）是使用批量方法制备的，这些方法的可扩展性很差，并且需要耗时的手动纯化程序。在这里，我们使用基于微流体的可扩展方法制备了基于聚乳酸（PLA）的聚合物纳米颗粒，并系统地研究了纯化方法（离心、切向流过滤（TFF））去除聚乙烯醇（PVA）对巨噬细胞摄取、抗炎作用、生物分布和蛋白质冠形成的影响。与离心法相比，TFF纯化显示出纳米颗粒的回收率显著更高，几乎没有观察到聚集现象。尽管TFF与之相当，但离心法去除PVA的效率更高。纳米颗粒的细胞结合、抗炎活性和生物分布研究表明，纯化方法会导致相关变化，这些变化与蛋白质冠谱相关。这项研究强调了TFF与微流体相结合作为一种高效、高产的纳米颗粒纯化方法的潜力，并揭示了在大规模开发纳米颗粒疗法时，除了物理化学性质外，还需要广泛确认纳米颗粒的生物活性。
