Belinky Thomas, El Amri Nouha, Lewis Parker K, Karakosta Allie, Pollard Rachel E, Pinkerton Nathalie M
Department of Chemical and Biomolecular Engineering, Tandon School of Engineering, New York University, NY, 11201, USA.
Department of Mechanical and Aerospace Engineering, Tandon School of Engineering, New York University, NY, 11201, USA.
Adv Mater Technol. 2025 Jan 8;10(1). doi: 10.1002/admt.202570002. Epub 2024 Aug 3.
Sequential NanoPrecipitation (SNaP) is a nascent controlled precipitation process for the tunable formation of polymeric particles for drug delivery and bioimaging. While SNaP relies on the same self-assembly principles as one-step Flash NanoPrecipitation, SNaP is a two-step assembly process in which the particle core is formed during a first mixing step followed by particle stabilization in a second mixing step. Decoupling the particle assembly steps improves control over the particle structure and, as we demonstrate for the first time, expands the attainable particle size range to include microparticles. Current SNaP experimental set-ups use commercial millifluidic mixers connected in series that suffer from several drawbacks including the inability to access short inter-mixer delay times. Here, we develop a robust 3D-printed, modular mixer design that enables access to short delay times (< 25 ms) not previously accessible. We prove empirically for the first time that the inter-mixer delay time is a key parameter for particle size control and that the nanoparticle size scales with delay time in agreement with Smoluchowski's model of diffusion-limited growth. We demonstrate the formation of polymeric particles ranging in size from 160 nm to 1.2 μm. Finally, we establish the versatility and applicability of our mixer design by encapsulating fluorophores and therapeutics into particles for the first time via SNaP.
连续纳米沉淀法(SNaP)是一种新兴的可控沉淀过程,用于可调谐地形成用于药物递送和生物成像的聚合物颗粒。虽然SNaP与一步法快速纳米沉淀法依赖相同的自组装原理,但SNaP是一个两步组装过程,其中颗粒核心在第一步混合过程中形成,随后在第二步混合过程中实现颗粒稳定化。将颗粒组装步骤解耦可改善对颗粒结构的控制,并且正如我们首次证明的那样,可将可达到的颗粒尺寸范围扩大到包括微粒。当前的SNaP实验装置使用串联连接的商用微流体混合器,这些混合器存在几个缺点,包括无法实现短的混合器间延迟时间。在此,我们开发了一种坚固的3D打印模块化混合器设计,能够实现以前无法达到的短延迟时间(<25毫秒)。我们首次通过实验证明,混合器间延迟时间是控制颗粒尺寸的关键参数,并且纳米颗粒尺寸与延迟时间成比例,这与斯莫卢霍夫斯基的扩散限制生长模型一致。我们展示了尺寸范围从160纳米到1.2微米的聚合物颗粒的形成。最后,我们通过首次通过SNaP将荧光团和治疗剂封装到颗粒中,确立了我们混合器设计的通用性和适用性。
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