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10.1016/j.ejpb.2021.03.004

http://scihub22266oqcxt.onion/10.1016/j.ejpb.2021.03.004
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33745980!ä!33745980

suck abstract from ncbi


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pmid33745980      Eur+J+Pharm+Biopharm 2021 ; 163 (ä): 252-265
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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 #MMPMID33745980
  • Mildner R; Hak S; Parot J; Hyldbakk A; Borgos SE; Some D; Johann C; Caputo F
  • Eur J Pharm Biopharm 2021[Jun]; 163 (ä): 252-265 PMID33745980show ga
  • 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.
  • |Drug Carriers/*chemistry[MESH]
  • |Fractionation, Field Flow/methods[MESH]
  • |Humans[MESH]
  • |Lipids/*chemistry[MESH]
  • |Nanomedicine/methods[MESH]
  • |Nanoparticles/*chemistry[MESH]
  • |Particle Size[MESH]
  • |Pharmaceutical Preparations/administration & dosage/chemistry[MESH]


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