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Optimization of DOTAP/chol Cationic Lipid Nanoparticles for mRNA, pDNA, and Oligonucleotide Delivery.
Sun, Mengwei; Dang, Utkarsh J; Yuan, Yuhao; Psaras, Alexandra Maria; Osipitan, Ositomiwa; Brooks, Tracy A; Lu, Fake; Di Pasqua, Anthony J.
  • Sun M; Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Binghamton University, Johnson City, NY, 13790, USA.
  • Dang UJ; Department of Biomedical Engineering, The Thomas J. Watson College of Engineering and Applied Science, Binghamton University, Binghamton, NY, 13902, USA.
  • Yuan Y; Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Binghamton University, Johnson City, NY, 13790, USA.
  • Psaras AM; Department of Health Sciences, Carleton University, Ottawa, Canada.
  • Osipitan O; 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 Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Binghamton University, Johnson City, NY, 13790, USA.
  • Di Pasqua AJ; Department of Biomedical Engineering, The Thomas J. Watson College of Engineering and Applied Science, Binghamton University, Binghamton, NY, 13902, USA.
AAPS PharmSciTech ; 23(5): 135, 2022 May 09.
Article in English | MEDLINE | ID: covidwho-1833435
ABSTRACT
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, 13 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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Nanoparticles / COVID-19 Type of study: Prognostic study Topics: Vaccines Limits: Humans Language: English Journal: AAPS PharmSciTech Journal subject: Pharmacology Year: 2022 Document Type: Article Affiliation country: S12249-022-02294-w

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Nanoparticles / COVID-19 Type of study: Prognostic study Topics: Vaccines Limits: Humans Language: English Journal: AAPS PharmSciTech Journal subject: Pharmacology Year: 2022 Document Type: Article Affiliation country: S12249-022-02294-w