Matthew Saphia A L, Totten John D, Phuagkhaopong Suttinee, Egan Gemma, Witte Kimia, Perrie Yvonne, Seib F Philipp
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, U.K.
EPSRC Future Manufacturing Research Hub for Continuous Manufacturing and Advanced Crystallisation (CMAC), University of Strathclyde, Technology and Innovation Centre, 99 George Street, Glasgow G1 1RD, U.K.
ACS Biomater Sci Eng. 2020 Dec 14;6(12):6748-6759. doi: 10.1021/acsbiomaterials.0c01028. Epub 2020 Nov 3.
Silk nanoparticles have demonstrated utility across a range of biomedical applications, especially as drug delivery vehicles. Their fabrication by bottom-up methods such as nanoprecipitation, rather than top-down manufacture, can improve critical nanoparticle quality attributes. Here, we establish a simple semi-batch method using drop-by-drop nanoprecipitation at the lab scale that reduces special-cause variation and improves mixing efficiency. The stirring rate was an important parameter affecting nanoparticle size and yield (400 < 200 < 0 rpm), while the initial dropping height (5.5 vs 7.5 cm) directly affected nanoparticle yield. Varying the nanoparticle standing time in the mother liquor between 0 and 24 h did not significantly affect nanoparticle physicochemical properties, indicating that steric and charge stabilizations result in high-energy barriers for nanoparticle growth. Manufacture across all tested formulations achieved nanoparticles between 104 and 134 nm in size with high β-sheet content, spherical morphology, and stability in aqueous media for over 1 month at 4 °C. This semi-automated drop-by-drop, semi-batch silk desolvation offers an accessible, higher-throughput platform for standardization of parameters that are difficult to control using manual methodologies.
丝绸纳米颗粒已在一系列生物医学应用中展现出实用性，尤其是作为药物递送载体。通过诸如纳米沉淀等自下而上的方法而非自上而下的制造方式来制备它们，可以改善关键的纳米颗粒质量属性。在此，我们在实验室规模建立了一种简单的半间歇方法，即逐滴纳米沉淀法，该方法减少了特殊原因变异并提高了混合效率。搅拌速率是影响纳米颗粒尺寸和产率的重要参数（400 < 200 < 0 rpm），而初始滴加高度（5.5 与 7.5 厘米）直接影响纳米颗粒产率。将纳米颗粒在母液中的静置时间在 0 至 24 小时之间变化，对纳米颗粒的物理化学性质没有显著影响，这表明空间位阻和电荷稳定作用为纳米颗粒生长形成了高能垒。所有测试配方制备出的纳米颗粒尺寸在 104 至 134 纳米之间，具有高β - 折叠含量、球形形态，并且在 4℃的水性介质中可稳定存在超过 1 个月。这种半自动逐滴半间歇式丝绸去溶剂化方法为标准化那些使用手动方法难以控制的参数提供了一个易于使用、高通量的平台。
