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Deagglomeration of DNA nanomedicine carriers using controlled ultrasonication

Hinchliffe, B; Turner, P; Cant, D J H; de Santis, E; Aggarwal, P; Harris, R; Templeton, D; Shard, A G; Hodnett, M; Minelli, C (2022) Deagglomeration of DNA nanomedicine carriers using controlled ultrasonication. Ultrasonics Sonochemistry, 89. 106141

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Control over the agglomeration state of manufactured particle systems for drug and oligonucleotide intracellular delivery is paramount to ensure reproducible and scalable therapeutic efficacy. Ultrasonication is a well-established mechanism for the deagglomeration of bulk powders in dispersion. Its use in manufacturing requires strict control of the uniformity of its cavitation field over the sample volume to minimise within-batch and batch-to-batch variability. In this work, we demonstrate the use of a multi-frequency reference cavitating vessel producing stable and reproducible cavitation fields to assist the controlled deagglomeration of a novel non-viral particle-based plasmid delivery system. This consists of the Nuvec delivery platform, comprising polyethylenimine-coated spiky silica particles with diameters of about 200 nm. We evaluated the use of controlled cavitation at different input powers and stages of preparation, for example before and after the plasmid loading. Plasmid loading was confirmed by X-ray photoelectron spectroscopy and gel electrophoresis. The latter was also used to assess plasmid integrity and the ability of the Nuvec particles to protect plasmid from potential degradation caused by the deagglomeration process. We show the utility of laser diffraction and differential centrifugal sedimentation in quantifying the efficacy of product de-agglomeration in the microscale and nanoscale size range respectively. Transmission electron microscopy was used to assess potential damages to the silica particle structure due to the sonication process.

Item Type: Article
Keywords: Inertial cavitation; Deagglomeration; Plasmid; Nanotechnology; Nanoparticle; Delivery system
Subjects: Nanoscience > Surface and Nanoanalysis
Divisions: Chemical & Biological Sciences
Identification number/DOI: 10.1016/j.ultsonch.2022.106141
Last Modified: 21 Jun 2023 13:37
URI: http://eprintspublications.npl.co.uk/id/eprint/9760

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