دورية أكاديمية
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Optimization of DOTAP/chol Cationic Lipid Nanoparticles for mRNA, pDNA, and Oligonucleotide Delivery.

التفاصيل البيبلوغرافية
العنوان: Optimization of DOTAP/chol Cationic Lipid Nanoparticles for mRNA, pDNA, and Oligonucleotide Delivery.
المؤلفون: Sun M; Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Binghamton University, Johnson City, NY, 13790, USA.; Department of Biomedical Engineering, The Thomas J. Watson College of Engineering and Applied Science, Binghamton University, Binghamton, NY, 13902, USA., Dang UJ; Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Binghamton University, Johnson City, NY, 13790, USA.; Department of Health Sciences, Carleton University, Ottawa, Canada., Yuan Y; Department of Biomedical Engineering, The Thomas J. Watson College of Engineering and Applied Science, Binghamton University, Binghamton, NY, 13902, USA., Psaras AM; Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Binghamton University, Johnson City, NY, 13790, USA., Osipitan O; Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Binghamton University, Johnson City, NY, 13790, USA.; Department of Biomedical Engineering, The Thomas J. Watson College of Engineering and Applied Science, Binghamton University, Binghamton, NY, 13902, USA., Brooks TA; Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Binghamton University, Johnson City, NY, 13790, USA., Lu F; Department of Biomedical Engineering, The Thomas J. Watson College of Engineering and Applied Science, Binghamton University, Binghamton, NY, 13902, USA., Di Pasqua AJ; Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Binghamton University, Johnson City, NY, 13790, USA. dipasqua@binghamton.edu.; Department of Biomedical Engineering, The Thomas J. Watson College of Engineering and Applied Science, Binghamton University, Binghamton, NY, 13902, USA. dipasqua@binghamton.edu.
المصدر: AAPS PharmSciTech [AAPS PharmSciTech] 2022 May 09; Vol. 23 (5), pp. 135. Date of Electronic Publication: 2022 May 09.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Springer Country of Publication: United States NLM ID: 100960111 Publication Model: Electronic Cited Medium: Internet ISSN: 1530-9932 (Electronic) Linking ISSN: 15309932 NLM ISO Abbreviation: AAPS PharmSciTech Subsets: MEDLINE
أسماء مطبوعة: Publication: New York : Springer
Original Publication: Arlington, VA : American Association of Pharmaceutical Scientists, c2000-
مواضيع طبية MeSH: COVID-19* , Nanoparticles*, COVID-19 Vaccines ; Cations ; Cholesterol ; Fatty Acids, Monounsaturated ; Humans ; Liposomes ; Oligonucleotides ; Propane ; Quaternary Ammonium Compounds ; RNA, Messenger/genetics
مستخلص: Lipid nanoparticles (LNPs) can be used as delivery vehicles for nucleic acid biotherapeutics. In fact, LNPs are currently being used in the Pfizer/BioNTech and Moderna COVID-19 vaccines. Cationic LNPs composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)/cholesterol (chol) LNPs have been classified as one of the most efficient gene delivery systems and are being tested in numerous clinical trials. The objective of this study was to examine the effect of the molar ratio of DOTAP/chol, PEGylation, and lipid to mRNA ratio on mRNA transfection, and explore the applications of DOTAP/chol LNPs in pDNA and oligonucleotide transfection. Here we showed that PEGylation significantly decreased mRNA transfection efficiency of DOTAP/chol LNPs. Among non-PEGylated LNP formulations, 1:3 molar ratio of DOTAP/chol in DOTAP/chol LNPs showed the highest mRNA transfection efficiency. Furthermore, the optimal ratio of DOTAP/chol LNPs to mRNA was tested to be 62.5 µM lipid to 1 μg mRNA. More importantly, these mRNA-loaded nanoparticles were stable for 60 days at 4 °C storage without showing reduction in transfection efficacy. We further found that DOTAP/chol LNPs were able to transfect pDNA and oligonucleotides, demonstrating the ability of these LNPs to transport the cargo into the cell nucleus. The influence of various factors in the formulation of DOTAP/chol cationic LNPs is thus described and will help improve drug delivery of nucleic acid-based vaccines and therapies.
(© 2022. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)
References: Biologicals. 2014 Sep;42(5):237-59. (PMID: 24996452)
Int J Mol Med. 2016 May;37(5):1345-54. (PMID: 26986502)
J Biol Chem. 1994 Jan 28;269(4):2550-61. (PMID: 8300583)
Nanomedicine. 2017 Aug;13(6):1869-1878. (PMID: 28434931)
Int J Mol Med. 2004 Oct;14(4):769-72. (PMID: 15375616)
Materials (Basel). 2021 Jan 16;14(2):. (PMID: 33466992)
ACS Nano. 2018 Oct 23;12(10):9830-9841. (PMID: 30253648)
Int J Nanomedicine. 2017 Oct 09;12:7323-7335. (PMID: 29070949)
Food Chem Toxicol. 2018 Mar;113:40-48. (PMID: 29337230)
Int J Pharm. 2010 May 10;390(2):198-207. (PMID: 20116418)
Pharmaceutics. 2020 Jan 28;12(2):. (PMID: 32013049)
Sci Rep. 2019 Oct 22;9(1):15120. (PMID: 31641141)
Adv Colloid Interface Sci. 2016 Jul;233:161-175. (PMID: 26265376)
J Control Release. 2004 Sep 30;99(2):329-37. (PMID: 15380641)
Molecules. 2021 Sep 13;26(18):. (PMID: 34577013)
Int J Nanomedicine. 2012;7:5577-91. (PMID: 23144561)
Int J Nanomedicine. 2012;7:393-401. (PMID: 22334773)
Mol Ther. 2005 May;11(5):801-10. (PMID: 15851018)
Nanomaterials (Basel). 2020 Jan 22;10(2):. (PMID: 31978968)
Biomed Pharmacother. 2018 Jul;103:982-988. (PMID: 29710515)
Int J Pharm. 2014 Nov 20;475(1-2):49-59. (PMID: 25138255)
Nat Rev Genet. 2014 Aug;15(8):541-55. (PMID: 25022906)
Adv Biomed Res. 2012;1:27. (PMID: 23210086)
Nat Rev Cancer. 2011 Mar;11(3):218-27. (PMID: 21346784)
Biochim Biophys Acta. 2008 Oct;1778(10):2177-81. (PMID: 18489900)
Autophagy. 2013 May;9(5):667-82. (PMID: 23422759)
Int J Nanomedicine. 2019 Jun 11;14:4353-4366. (PMID: 31354265)
Microb Pathog. 2017 Aug;109:200-208. (PMID: 28578092)
Pharmaceutics. 2020 Nov 29;12(12):. (PMID: 33260460)
Colloids Surf B Biointerfaces. 2013 Jan 1;101:6-13. (PMID: 22789783)
Adv Drug Deliv Rev. 2016 Apr 1;99(Pt A):28-51. (PMID: 26456916)
Biotechnol J. 2015 Sep;10(9):1370-89. (PMID: 26037687)
Int J Nanomedicine. 2010 Aug 09;5:371-83. (PMID: 20957159)
PLoS One. 2012;7(4):e34833. (PMID: 22558101)
Chem Phys Lipids. 2005 Jun;135(2):117-29. (PMID: 15921973)
World J Surg. 2009 Apr;33(4):685-97. (PMID: 19023615)
Nat Commun. 2016 Jun 06;7:11822. (PMID: 27264609)
معلومات مُعتمدة: R15 GM140444 United States GM NIGMS NIH HHS
فهرسة مساهمة: Keywords: DOTAP/cholesterol; LNP-mRNA; lipid nanoparticles; mRNA delivery; transfection efficiency
المشرفين على المادة: 0 (COVID-19 Vaccines)
0 (Cations)
0 (Fatty Acids, Monounsaturated)
0 (Lipid Nanoparticles)
0 (Liposomes)
0 (Oligonucleotides)
0 (Quaternary Ammonium Compounds)
0 (RNA, Messenger)
97C5T2UQ7J (Cholesterol)
MR86K0XRQP (1,2-dioleoyloxy-3-(trimethylammonium)propane)
T75W9911L6 (Propane)
تواريخ الأحداث: Date Created: 20220509 Date Completed: 20220511 Latest Revision: 20221029
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC9084260
DOI: 10.1208/s12249-022-02294-w
PMID: 35534697
قاعدة البيانات: MEDLINE
الوصف
تدمد:1530-9932
DOI:10.1208/s12249-022-02294-w