Silk nanoparticle manufacture in semi-batch format

Saphia A. L. Matthew, John D. Totten, Suttinee Phuagkhaopong, Gemma Egan, Kimia Witte, Yvonne Perrie, F. Philipp Seib

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)
32 Downloads (Pure)


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.

Original languageEnglish
Pages (from-to)6748-6759
Number of pages12
JournalACS Biomaterials Science & Engineering
Issue number12
Early online date3 Nov 2020
Publication statusPublished - 14 Dec 2020


  • silk fibroin
  • nanoprecipitation
  • desolvation
  • nanoparticle
  • biopolymer


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