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J Colloid Interface Sci. 2019 Jan 14;540:342-353. doi: 10.1016/j.jcis.2019.01.043. [Epub ahead of print]

Modifying internal organization and surface morphology of siRNA lipoplexes by sodium alginate addition for efficient siRNA delivery.

Author information

1
Faculdade de Farmácia, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil; CNRS, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS), UMR 8258, F-75006 Paris, France; INSERM, UTCBS U 1022, F-75006 Paris, France; Université Paris Descartes, Sorbonne-Paris-Cité University, UTCBS, F-75006 Paris, France; Chimie ParisTech, PSL Research University, UTCBS, F-75005 Paris, France.
2
Centro de Desenvolvimento da Tecnologia Nuclear, CDTN, 31270-091 Belo Horizonte, MG, Brazil.
3
CNRS, Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), UMR 7590, F-75005 Paris, France; Sorbonne Université, IMPMC, F-75005 Paris, France; IRD, IMPMC, F-75005 Paris, France; MNHN, IMPMC, F-75005 Paris, France.
4
Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, University of Chile, 8380000 Santiago, Chile; INSERM, UMR 957, Equipe Labellisée LIGUE 2012, F-44035 Nantes, France; Université de Nantes, Nantes Atlantique Universités, Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Faculté de Médecine, F-44035 Nantes, France.
5
INSERM, UMR 957, Equipe Labellisée LIGUE 2012, F-44035 Nantes, France; Université de Nantes, Nantes Atlantique Universités, Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Faculté de Médecine, F-44035 Nantes, France.
6
Faculdade de Farmácia, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil.
7
CNRS, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS), UMR 8258, F-75006 Paris, France; INSERM, UTCBS U 1022, F-75006 Paris, France; Université Paris Descartes, Sorbonne-Paris-Cité University, UTCBS, F-75006 Paris, France; Chimie ParisTech, PSL Research University, UTCBS, F-75005 Paris, France.
8
Departamento de Física, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil.
9
CNRS, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS), UMR 8258, F-75006 Paris, France; INSERM, UTCBS U 1022, F-75006 Paris, France; Université Paris Descartes, Sorbonne-Paris-Cité University, UTCBS, F-75006 Paris, France; Chimie ParisTech, PSL Research University, UTCBS, F-75005 Paris, France. Electronic address: virginie.escriou@parisdescartes.fr.

Abstract

Vectorized small interfering RNAs (siRNAs) are widely used to induce specific mRNA degradation in the intracellular compartment of eukaryotic cells. Recently, we developed efficient cationic lipid-based siRNA vectors (siRNA lipoplexes or siLex) containing sodium alginate (Nalg-siLex) with superior efficiency and stability properties than siLex. In this study, we assessed the physicochemical and some biological properties of Nalg-siLex compared to siLex. While no significant differences in size, ζ potential and siRNA compaction were detected, the addition of sodium alginate modified the particle morphology, producing smoother and heterogeneous particles characterized by transmission electron microscopy. We also noted that Nalg-siLex have surface differences observed by X-ray photoelectron spectroscopy. These differences could arise from an internal reorganization of components induced by the addition of sodium alginate, that is indicated by Small-Angle X-ray Scattering results. Moreover, Nalg-siLex did not trigger significant hepatotoxicity nor inflammatory cytokine secretion compared to siLex. Taken together these results suggest that sodium alginate played a key role by structuring and reinforcing siRNA lipoplexes, leading to more stable and efficient delivery vector.

KEYWORDS:

Anionic polymer; Cationic lipid; Delivery system; Nanoparticle; RNA interference; Structure

PMID:
30660791
DOI:
10.1016/j.jcis.2019.01.043

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