Spheroplexes: Hybrid PLGA-cationic lipid nanoparticles, for in vitro and oral delivery of siRNA.

Autor: Arruda DC; Université Paris Cité, CNRS, INSERM, UTCBS, F-75006 Paris, France; Faculdade de Farmácia, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil. Electronic address: danielle.campiol-arruda@univ-lyon1.fr., Lachagès AM; Université Paris Cité, CNRS, INSERM, UTCBS, F-75006 Paris, France., Demory H; Université Paris Cité, CNRS, INSERM, UTCBS, F-75006 Paris, France., Escriou G; Université Paris Cité, CNRS, INSERM, UTCBS, F-75006 Paris, France., Lai-Kuen R; Cellular and Molecular Imaging Platform, US 25 Inserm, UMS 3612 CNRS, Faculté de Pharmacie de Paris, Université Paris Cité, F-75006 Paris, France., Dugas PY; Université de Lyon, Université Claude Bernard Lyon 1, CPE Lyon, CNRS, UMR 5128, Laboratoire Catalyse, Polymérisation, Procédés et Matériaux (CP2M), 69616 Villeurbanne, France., Hoffmann C; Université Paris Cité, CNRS, INSERM, UTCBS, F-75006 Paris, France., Bessoles S; Université Paris Cité, CNRS, INSERM, UTCBS, F-75006 Paris, France., Sarrabayrouse G; Université Paris Cité, CNRS, INSERM, UTCBS, F-75006 Paris, France., Malachias A; Departamento de Física, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil., Finet S; Institut de Minéralogie, de Physique des Matériaux et de Cosmochimie, Sorbonne Université, UMR CNRS 7590, MNHN, 75252 Paris, France., Gastelois PL; Centro de Desenvolvimento da Tecnologia Nuclear, CDTN, 31270-901 Belo Horizonte, MG, Brazil., de Almeida Macedo WA; Centro de Desenvolvimento da Tecnologia Nuclear, CDTN, 31270-901 Belo Horizonte, MG, Brazil., da Silva Cunha A Jr; Faculdade de Farmácia, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil., Bigey P; Université Paris Cité, CNRS, INSERM, UTCBS, F-75006 Paris, France; ChimieParisTech, PSL University, F-75005 Paris, France., Escriou V; Université Paris Cité, CNRS, INSERM, UTCBS, F-75006 Paris, France.
Jazyk: angličtina
Zdroj: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2022 Oct; Vol. 350, pp. 228-243. Date of Electronic Publication: 2022 Aug 24.
DOI: 10.1016/j.jconrel.2022.08.030
Abstrakt: Vectorized small interfering RNAs (siRNAs) are widely used to induce gene silencing. Among the delivery systems used, lipid-based particles are the most effective. Our objective was the development of novel lipid-polymer hybrid nanoparticles, from lipoplexes (complexes of cationic lipid and siRNAs), and poly (lactic-co-glycolic acid) (PLGA), using a simple modified nanoprecipitation method. Due to their morphology, we called these hybrid nanoparticles Spheroplexes. We elucidated their structure using several physico-chemical techniques and showed that they are composed of a hydrophobic PLGA matrix, surrounded by a lipid envelope adopting a lamellar structure, in which the siRNA is complexed, and they retain surface characteristics identical to the starting nanoparticles, i.e. lipoplexes siRNA. We analyzed the composition of the particle population and determined the final percentage of spheroplexes within this population, 80 to 85% depending on the preparation conditions, using fluorescent markers and the ability of flow cytometry to detect nanometric particles (approximately 200 nm). Finally, we showed that spheroplexes are very stable particles and more efficient than siRNA lipoplexes for the delivery of siRNA to cultured cells. We administered spheroplexes contain siRNAs targeting TNF-α to mice with ulcerative colitis induced by dextran sulfate and our results indicate a disease regression effect with a response probably mediated by their uptake by macrophages / monocytes at the level of lamina propria of the colon. The efficacy of decreased level of TNF-α in vivo seemed to be an association of spheroplexes polymer-lipid composition and the specific siRNA. These results demonstrate that spheroplexes are a promising hybrid nanoparticle for the oral delivery of siRNA to the colon.
Competing Interests: Declaration of Competing Interest None.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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