Silk nanoparticle manufacture in semi-batch format

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Matthew, Saphia A. L. and Totten, John D. and Phuagkhaopong, Suttinee and Egan, Gemma and Witte, Kimia and Perrie, Yvonne and Seib, F. Philipp (2020) Silk nanoparticle manufacture in semi-batch format. ACS Biomaterials Science & Engineering, 6 (12). pp. 6748-6759. ISSN 2373-9878 (https://doi.org/10.1021/acsbiomaterials.0c01028)

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Abstract

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.

ORCID iDs

Matthew, Saphia A. L., Totten, John D. ORCID logoORCID: https://orcid.org/0000-0001-9665-1569, Phuagkhaopong, Suttinee, Egan, Gemma, Witte, Kimia ORCID logoORCID: https://orcid.org/0000-0003-4708-1621, Perrie, Yvonne and Seib, F. Philipp ORCID logoORCID: https://orcid.org/0000-0002-1955-1975;
CORE (COnnecting REpositories)