Encapsulation of Dexamethasone into mRNA–Lipid Nanoparticles Is a Promising Approach for the Development of Liver-Targeted Anti-Inflammatory Therapies
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| Publicat a: | International Journal of Molecular Sciences vol. 25, no. 20 (2024), p. 11254 |
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| Autor principal: | |
| Altres autors: | , , , , , , , , , , , |
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MDPI AG
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| Accés en línia: | Citation/Abstract Full Text + Graphics Full Text - PDF |
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| 003 | UK-CbPIL | ||
| 022 | |a 1661-6596 | ||
| 022 | |a 1422-0067 | ||
| 024 | 7 | |a 10.3390/ijms252011254 |2 doi | |
| 035 | |a 3120650592 | ||
| 045 | 2 | |b d20241015 |b d20241031 | |
| 084 | |a 231645 |2 nlm | ||
| 100 | 1 | |a Ignacio Rivero Berti |u Children’s Hospital, University Medical Center of the Johannes Gutenberg University, Langenbeckstr. 1, 55131 Mainz, Germany; <email>ignaciob@uni-mainz.de</email> (I.R.B.); <email>gambaror@uni-mainz.de</email> (R.C.G.); <email>mj.limeres@uni-mainz.de</email> (M.J.L.); <email>malin.svensson@uni-mainz.de</email> (M.S.); <email>fraudesi@uni-mainz.de</email> (S.F.-E.G.); <email>pretsch@uni-mainz.de</email> (L.P.); <email>maximilianocacicedo@gmail.com</email> (M.L.C.); CINDEFI—Centro de Investigación y Desarrollo en Fermentaciones Industriales, Laboratorio de Nanobiomateriales, Facultad de Ciencias Exactas, Universidad Nacional de La Plata (UNLP)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), La Plata 1900, Argentina | |
| 245 | 1 | |a Encapsulation of Dexamethasone into mRNA–Lipid Nanoparticles Is a Promising Approach for the Development of Liver-Targeted Anti-Inflammatory Therapies | |
| 260 | |b MDPI AG |c 2024 | ||
| 513 | |a Journal Article | ||
| 520 | 3 | |a The objective of this study was to develop two lipid nanoparticle (LNP) formulations capable of efficiently expressing a reporter mRNA while co-delivering the anti-inflammatory drug dexamethasone (DX) to reduce inflammatory side effects in protein replacement therapies. Two types of LNPs were developed, in which 25% of cholesterol was replaced by DX. These LNPs contained either 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) or 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) as a helper lipid. The resulting LNPs exhibited high stability, homogeneity, and near-neutral Zeta potentials. SAXS experiments confirmed DX incorporation into the LNP core, with slow in vitro DX release observed over 48 h. The LNPs achieved high mRNA encapsulation efficiency (95–100%) and effectively transfected HepG2 cells, dendritic cells, and hPBMCs. While LNPs increased cytokine release (IL-1β, TNF-α, MCP-1), LNPs-DX significantly reduced cytokine levels, demonstrating enhanced anti-inflammatory properties while maintaining mRNA expression levels. In vivo biodistribution showed predominant liver localization post-intramuscular injection, regardless of the DSPC or DOPE composition. LNPs co-loaded with mRNA and DX are promising candidates for continuous protein replacement. Due to their ability to reduce treatment-related inflammation while maintaining significant mRNA expression levels, these LNPs are perfectly suited for the treatment of liver-related metabolic diseases. | |
| 651 | 4 | |a Canada | |
| 653 | |a Thymus gland | ||
| 653 | |a Pharmacokinetics | ||
| 653 | |a Vaccines | ||
| 653 | |a Lipids | ||
| 653 | |a Polyethylene glycol | ||
| 653 | |a Efficiency | ||
| 653 | |a Cytokines | ||
| 653 | |a Cholesterol | ||
| 653 | |a Medical research | ||
| 700 | 1 | |a Gambaro, Rocío Celeste |u Children’s Hospital, University Medical Center of the Johannes Gutenberg University, Langenbeckstr. 1, 55131 Mainz, Germany; <email>ignaciob@uni-mainz.de</email> (I.R.B.); <email>gambaror@uni-mainz.de</email> (R.C.G.); <email>mj.limeres@uni-mainz.de</email> (M.J.L.); <email>malin.svensson@uni-mainz.de</email> (M.S.); <email>fraudesi@uni-mainz.de</email> (S.F.-E.G.); <email>pretsch@uni-mainz.de</email> (L.P.); <email>maximilianocacicedo@gmail.com</email> (M.L.C.) | |
| 700 | 1 | |a Limeres, María José |u Children’s Hospital, University Medical Center of the Johannes Gutenberg University, Langenbeckstr. 1, 55131 Mainz, Germany; <email>ignaciob@uni-mainz.de</email> (I.R.B.); <email>gambaror@uni-mainz.de</email> (R.C.G.); <email>mj.limeres@uni-mainz.de</email> (M.J.L.); <email>malin.svensson@uni-mainz.de</email> (M.S.); <email>fraudesi@uni-mainz.de</email> (S.F.-E.G.); <email>pretsch@uni-mainz.de</email> (L.P.); <email>maximilianocacicedo@gmail.com</email> (M.L.C.) | |
| 700 | 1 | |a Huck-Iriart, Cristián |u ALBA Synchrotron Light Source, Carrer de la Llum 2–26, Cerdanyola del Vallès, 08290 Barcelona, Spain; <email>chuck@cells.es</email> | |
| 700 | 1 | |a Svensson, Malin |u Children’s Hospital, University Medical Center of the Johannes Gutenberg University, Langenbeckstr. 1, 55131 Mainz, Germany; <email>ignaciob@uni-mainz.de</email> (I.R.B.); <email>gambaror@uni-mainz.de</email> (R.C.G.); <email>mj.limeres@uni-mainz.de</email> (M.J.L.); <email>malin.svensson@uni-mainz.de</email> (M.S.); <email>fraudesi@uni-mainz.de</email> (S.F.-E.G.); <email>pretsch@uni-mainz.de</email> (L.P.); <email>maximilianocacicedo@gmail.com</email> (M.L.C.) | |
| 700 | 1 | |a Silvia Fraude-El Ghazi |u Children’s Hospital, University Medical Center of the Johannes Gutenberg University, Langenbeckstr. 1, 55131 Mainz, Germany; <email>ignaciob@uni-mainz.de</email> (I.R.B.); <email>gambaror@uni-mainz.de</email> (R.C.G.); <email>mj.limeres@uni-mainz.de</email> (M.J.L.); <email>malin.svensson@uni-mainz.de</email> (M.S.); <email>fraudesi@uni-mainz.de</email> (S.F.-E.G.); <email>pretsch@uni-mainz.de</email> (L.P.); <email>maximilianocacicedo@gmail.com</email> (M.L.C.) | |
| 700 | 1 | |a Pretsch, Leah |u Children’s Hospital, University Medical Center of the Johannes Gutenberg University, Langenbeckstr. 1, 55131 Mainz, Germany; <email>ignaciob@uni-mainz.de</email> (I.R.B.); <email>gambaror@uni-mainz.de</email> (R.C.G.); <email>mj.limeres@uni-mainz.de</email> (M.J.L.); <email>malin.svensson@uni-mainz.de</email> (M.S.); <email>fraudesi@uni-mainz.de</email> (S.F.-E.G.); <email>pretsch@uni-mainz.de</email> (L.P.); <email>maximilianocacicedo@gmail.com</email> (M.L.C.) | |
| 700 | 1 | |a Si, Shutian |u Max Planck Institute for Polymer Research, Department of Physical Chemistry of Polymers, Ackermannweg 10, 55128 Mainz, Germany; <email>sis2@mpip-mainz.mpg.de</email> (S.S.); <email>lieberw@mpip-mainz.mpg.de</email> (I.L.); <email>landfest@uni-mainz.de</email> (K.L.) | |
| 700 | 1 | |a Lieberwirth, Ingo |u Max Planck Institute for Polymer Research, Department of Physical Chemistry of Polymers, Ackermannweg 10, 55128 Mainz, Germany; <email>sis2@mpip-mainz.mpg.de</email> (S.S.); <email>lieberw@mpip-mainz.mpg.de</email> (I.L.); <email>landfest@uni-mainz.de</email> (K.L.) | |
| 700 | 1 | |a Landfester, Katharina |u Max Planck Institute for Polymer Research, Department of Physical Chemistry of Polymers, Ackermannweg 10, 55128 Mainz, Germany; <email>sis2@mpip-mainz.mpg.de</email> (S.S.); <email>lieberw@mpip-mainz.mpg.de</email> (I.L.); <email>landfest@uni-mainz.de</email> (K.L.) | |
| 700 | 1 | |a Cacicedo, Maximiliano Luis |u Children’s Hospital, University Medical Center of the Johannes Gutenberg University, Langenbeckstr. 1, 55131 Mainz, Germany; <email>ignaciob@uni-mainz.de</email> (I.R.B.); <email>gambaror@uni-mainz.de</email> (R.C.G.); <email>mj.limeres@uni-mainz.de</email> (M.J.L.); <email>malin.svensson@uni-mainz.de</email> (M.S.); <email>fraudesi@uni-mainz.de</email> (S.F.-E.G.); <email>pretsch@uni-mainz.de</email> (L.P.); <email>maximilianocacicedo@gmail.com</email> (M.L.C.) | |
| 700 | 1 | |a Germán Abel Islan |u Children’s Hospital, University Medical Center of the Johannes Gutenberg University, Langenbeckstr. 1, 55131 Mainz, Germany; <email>ignaciob@uni-mainz.de</email> (I.R.B.); <email>gambaror@uni-mainz.de</email> (R.C.G.); <email>mj.limeres@uni-mainz.de</email> (M.J.L.); <email>malin.svensson@uni-mainz.de</email> (M.S.); <email>fraudesi@uni-mainz.de</email> (S.F.-E.G.); <email>pretsch@uni-mainz.de</email> (L.P.); <email>maximilianocacicedo@gmail.com</email> (M.L.C.); CINDEFI—Centro de Investigación y Desarrollo en Fermentaciones Industriales, Laboratorio de Nanobiomateriales, Facultad de Ciencias Exactas, Universidad Nacional de La Plata (UNLP)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), La Plata 1900, Argentina | |
| 700 | 1 | |a Gehring, Stephan |u Children’s Hospital, University Medical Center of the Johannes Gutenberg University, Langenbeckstr. 1, 55131 Mainz, Germany; <email>ignaciob@uni-mainz.de</email> (I.R.B.); <email>gambaror@uni-mainz.de</email> (R.C.G.); <email>mj.limeres@uni-mainz.de</email> (M.J.L.); <email>malin.svensson@uni-mainz.de</email> (M.S.); <email>fraudesi@uni-mainz.de</email> (S.F.-E.G.); <email>pretsch@uni-mainz.de</email> (L.P.); <email>maximilianocacicedo@gmail.com</email> (M.L.C.) | |
| 773 | 0 | |t International Journal of Molecular Sciences |g vol. 25, no. 20 (2024), p. 11254 | |
| 786 | 0 | |d ProQuest |t Health & Medical Collection | |
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