Characterization of positively charged polyplexes by tunable resistive pulse sensing.

Eur J Pharm Biopharm

Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians Universität München, 81377 Munich, Germany. Electronic address:

Published: January 2021

AI Article Synopsis

  • Non-viral siRNA delivery has gained traction due to the approval of siRNA-based drugs, with lipid and polymer formulations being key in research.
  • Characterizing the size and properties of polydisperse nanoparticles poses challenges, particularly for positively charged particles, which current methods struggle to measure effectively.
  • This article introduces a new coating solution using choline-chloride, enabling accurate particle measurement of positively charged siRNA formulations and laying the groundwork for better characterization of similar nanoparticle systems.

Article Abstract

With the approval of the first siRNA-based drugs, non-viral siRNA delivery has gained special interest in industry and academia in the last two years. For non-viral delivery, positively charged lipid and polymer formulations play a central role in research and development. However, nanoparticle size characterization, particularly of polydisperse formulations, can be very challenging. Tunable resistive pulse sensing for particle by particle measurements of size, polydispersity, zeta potential and a direct concentration promises better assessment of nanoparticle formulations. However, the current application is not optimized for positively charged particles. A supplier-provided coating solution for difficult-to-measure samples does not allow for successful measurements of positively charged nanoparticles. This article describes a new coating solution based on choline-chloride. Coating is verified by current-voltage (I-V) recordings and ultimately tested on a positively charged nanoparticle formulation comprising of siRNA and PEG-PCL-PEI polymer. This coating allows successful size, polydispersity index (PDI) and concentration measurement by tunable resistive pulse sensing of positively charged PEI-based polyplexes. This article provides the foundation for further characterization of polyplexes as well as other positively charged nanoparticle formulations based on particle by particle measurements.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116642PMC
http://dx.doi.org/10.1016/j.ejpb.2020.12.010DOI Listing

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