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Improved multidetector asymmetrical-flow field-flow fractionation method for particle sizing and concentration measurements of lipid-based nanocarriers for RNA delivery.
Mildner, R; Hak, S; Parot, J; Hyldbakk, A; Borgos, S E; Some, D; Johann, C; Caputo, F.
  • Mildner R; Wyatt Technology, Hochstrasse 12a, 56307 Dernbach, Germany.
  • Hak S; Department of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim, Norway.
  • Parot J; Department of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim, Norway.
  • Hyldbakk A; Department of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim, Norway.
  • Borgos SE; Department of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim, Norway.
  • Some D; Wyatt Technology, 6330 Hollister Ave., Santa Barbara, CA 93117, USA.
  • Johann C; Wyatt Technology, Hochstrasse 12a, 56307 Dernbach, Germany.
  • Caputo F; Department of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim, Norway. Electronic address: fanny.caputo@sintef.no.
Eur J Pharm Biopharm ; 163: 252-265, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1144592
ABSTRACT
Lipid-based nanoparticles for RNA delivery (LNP-RNA) are revolutionizing the nanomedicine field, with one approved gene therapy formulation and two approved vaccines against COVID-19, as well as multiple ongoing clinical trials. As for other innovative nanopharmaceuticals (NPhs), the advancement of robust methods to assess their quality and safety profiles-in line with regulatory needs-is critical for facilitating their development and clinical translation. Asymmetric-flow field-flow fractionation coupled to multiple online optical detectors (MD-AF4) is considered a very versatile and robust approach for the physical characterisation of nanocarriers, and has been used successfully for measuring particle size, polydispersity and physical stability of lipid-based systems, including liposomes and solid lipid nanoparticles. However, the unique core structure of LNP-RNA, composed of ionizable lipids electrostatically complexed with RNA, and the relatively labile lipid-monolayer coating, is more prone to destabilization during focusing in MD-AF4 than previously characterised nanoparticles, resulting in particle aggregation and sample loss. Hence characterisation of LNP-RNA by MD-AF4 needs significant adaptation of the methods developed for liposomes. To improve the performance of MD-AF4 applied to LNP-RNA in a systematic and comprehensive manner, we have explored the use of the frit-inlet channel where, differently from the standard AF4 channel, the particles are relaxed hydrodynamically as they are injected. The absence of a focusing step minimizes contact between the particle and the membrane, reducing artefacts (e.g. sample loss, particle aggregation). Separation in a frit-inlet channel enables satisfactory reproducibility and acceptable sample recovery in the commercially available MD-AF4 instruments. In addition to slice-by-slice measurements of particle size, MD-AF4 also allows to determine particle concentration and the particle size distribution, demonstrating enhanced versatility beyond standard sizing measurements.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA / Drug Carriers / Nanoparticles / Lipids Type of study: Prognostic study / Systematic review/Meta Analysis Topics: Vaccines Limits: Humans Language: English Journal: Eur J Pharm Biopharm Journal subject: Pharmacy / Pharmacology Year: 2021 Document Type: Article Affiliation country: J.ejpb.2021.03.004

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Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA / Drug Carriers / Nanoparticles / Lipids Type of study: Prognostic study / Systematic review/Meta Analysis Topics: Vaccines Limits: Humans Language: English Journal: Eur J Pharm Biopharm Journal subject: Pharmacy / Pharmacology Year: 2021 Document Type: Article Affiliation country: J.ejpb.2021.03.004