Development of an imaged capillary isoelectric focusing method for characterizing the surface charge of mRNA lipid nanoparticle vaccines.
Cationic lipid
Imaged capillary isoelectric focusing
Isoelectric point (pI)
Lipid nanoparticles
Maurice
mRNA vaccine
Journal
Electrophoresis
ISSN: 1522-2683
Titre abrégé: Electrophoresis
Pays: Germany
ID NLM: 8204476
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
27
01
2019
revised:
09
06
2019
accepted:
10
06
2019
pubmed:
21
6
2019
medline:
5
3
2020
entrez:
21
6
2019
Statut:
ppublish
Résumé
Lipid nanoparticles (LNPs) have been employed for drug delivery in small molecules, siRNA, mRNA, and pDNA for both therapeutics and vaccines. Characterization of LNPs is challenging because they are heterogeneous mixtures of large complex particles. Many tools for particle size characterization, such as dynamic and static light scattering, have been applied as well as morphology analysis using electron microscopy. CE has been applied for the characterization of many different large particles such as liposomes, polymer, and viruses. However, there have been limited efforts to characterize the surface charge of LNPs and CIEF has not been explored for this type of particle. Typically, LNPs for delivery of oligonucleotides contain at least four different lipids, with at least one being an ionizable cationic lipid. Here, we describe the development of an imaged capillary isoelectric focusing method used to measure the surface charge (i.e., pI) of an LNP-based mRNA vaccine. This method is capable of distinguishing the pI of LNPs manufactured with one or more different ionizable lipids for the purpose of confirming LNP identity in a manufacturing setting. Additionally, the method is quantitative and stability-indicating making it suitable for both process and formulation development.
Identifiants
pubmed: 31218707
doi: 10.1002/elps.201900063
pmc: PMC6771570
doi:
Substances chimiques
Lipids
0
RNA, Messenger
0
Vaccines, Synthetic
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2602-2609Informations de copyright
© 2019 The Authors. Electrophoresis published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Références
Chem Commun (Camb). 2005 Feb 14;(6):787-8
pubmed: 15685338
Anal Biochem. 2017 Oct 1;534:19-23
pubmed: 28666777
J Chromatogr A. 2016 Sep 9;1463:169-75
pubmed: 27543386
Electrophoresis. 2001 Apr;22(7):1305-13
pubmed: 11379952
Nanomedicine. 2013 Feb;9(2):233-46
pubmed: 22698807
Electrophoresis. 2012 Jun;33(11):1538-44
pubmed: 22736354
Expert Rev Vaccines. 2015 Feb;14(2):221-34
pubmed: 25540984
Electrophoresis. 2006 Feb;27(4):852-8
pubmed: 16411278
Curr Top Med Chem. 2012;12(2):97-107
pubmed: 22196274
Mol Ther. 2010 Jan;18(1):171-80
pubmed: 19738601
Cancer Res. 1990 Feb 1;50(3):575-9
pubmed: 2297698
Front Immunol. 2017 Feb 06;8:69
pubmed: 28220118
Pharm Res. 2005 Mar;22(3):362-72
pubmed: 15835741
J Chromatogr A. 1998 Aug 21;817(1-2):163-71
pubmed: 9764490
Gene Ther. 2017 Mar;24(3):133-143
pubmed: 28094775
Electrophoresis. 2005 Feb;26(4-5):735-751
pubmed: 15714573
Talanta. 2015 Nov 1;144:1030-5
pubmed: 26452923
Anal Chem. 2012 Jul 17;84(14):6088-96
pubmed: 22816783
Science. 2004 Mar 19;303(5665):1818-22
pubmed: 15031496
Mol Pharm. 2014 Nov 3;11(11):4143-53
pubmed: 25317715
J Chromatogr B Analyt Technol Biomed Life Sci. 2004 Feb 5;800(1-2):7-25
pubmed: 14698231
Int J Nanomedicine. 2016 Jul 05;11:3077-86
pubmed: 27462152
Biomaterials. 2010 Sep;31(26):6867-75
pubmed: 20541799
N Engl J Med. 2018 Jul 5;379(1):11-21
pubmed: 29972753
Mol Ther. 2014 Dec;22(12):2118-2129
pubmed: 25027661
Mol Pharm. 2013 Jan 7;10(1):397-405
pubmed: 23210488
Electrophoresis. 2014 Apr;35(7):1072-8
pubmed: 24812686