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Chitosan-lipid nanoparticles (CS-LNPs): Application to siRNA delivery

Abstract : To benefit from the biocompatibility of lipid nanoparticles associated with the transfection ability of chitosan, small chitosan lipid nanoparticles (CS-LNPs) dedicated to SiRNA delivery were formulated by an easy-to-implement one-step process. Formulations of CS-LNP5 (lipid core stabilized by a shell comprising phospholipids/cationic lipids and hydrophobically modified chitosan) were optimized for their physicochemical properties (size, zeta potential, colloidal stability) according to their shell composition. In particular, amphiphilic chitosan with various molecular weight and C12 degrees of substitution, and different phospholipids and cationic lipids (lecithin, DOTAP, DOPE) were included at the particle surface at different ratios. The ability of the particles for SiRNA complexation, NIH3T3 cell transfection, and ERK1 downregulation, were studied. Lipid nanoparticles formulated with 15,000 g/mol 2% C12 substituted chitosan, DOTAP and DOPE, mediated 40% ERK1 downregulation efficiency, comparable to lipofectamin (TM) RNAimax, while displaying no cytotoxicity up to 500 mu g/mL.
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Submitted on : Monday, July 15, 2019 - 4:26:58 PM
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Ozgul Tezgel, Anna Szarpak-Jankowska, Amandine Arnould, Rachel Auzély-Velty, Isabelle Texier. Chitosan-lipid nanoparticles (CS-LNPs): Application to siRNA delivery. Journal of Colloid and Interface Science, Elsevier, 2018, 510, pp.45-56. ⟨10.1016/j.jcis.2017.09.045⟩. ⟨cea-02183867⟩



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