Lyophilisation and concentration of chitosan/siRNA polyplexes: Influence of buffer composition, oligonucleotide sequence, and hyaluronic acid coating

Journal of Colloid and Interface Science
Daniel VeilleuxMichael D Buschmann

Abstract

Chitosan (CS)/siRNA polyplexes have great therapeutic potential for treating multiple diseases by gene silencing. However, clinical application of this technology requires the development of concentrated, hemocompatible, pH neutral formulations for safe and efficient administration. In this study we evaluate physicochemical properties of chitosan polyplexes in various buffers at increasing ionic strengths, to identify conditions for freeze-drying and rehydration at higher doses of uncoated or hyaluronic acid (HA)-coated polyplexes while maintaining physiological compatibility. Optimized formulations are used to evaluate the impact of the siRNA/oligonucleotide sequence on polyplex physicochemical properties, and to measure their in vitro silencing efficiency, cytotoxicity, and hemocompatibility. Specific oligonucleotide sequences influence polyplex physical properties at low N:P ratios, as well as their stability during freeze-drying. Nanoparticles display greater stability for oligodeoxynucleotides ODN vs siRNA; AT-rich vs GC-rich; and overhangs vs blunt ends. Using this knowledge, various CS/siRNA polyplexes are prepared with and without HA coating, freeze-dried and rehydrated at increased concentrations using reduced rehydrat...Continue Reading

Citations

May 24, 2018·Artificial Cells, Nanomedicine, and Biotechnology·Nana LiNianping Feng
Mar 29, 2019·Journal of Cellular Physiology·Shahin AghamiriBabak Negahdari
Aug 2, 2019·Nanomedicine·Shahin AghamiriNima Rezaei
Nov 7, 2019·Drug Development Research·Kamal DuaDinesh Kumar Chellappan
Jul 18, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Inés Serrano-SevillaJesús M de la Fuente
Jan 1, 2020·Journal of Pharmaceutical Sciences·Ousamah Younoss SolimanMarc Lavertu
May 4, 2020·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Kevin Ita
May 4, 2021·Chemical Reviews·Ramya KumarTheresa M Reineke
May 31, 2021·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Eduard Trenkenschuh, Wolfgang Friess
Nov 7, 2021·Advanced Healthcare Materials·Evan Kurt, Tatiana Segura

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