Nucleic Acid (NA) based therapeutics are poised to disrupt modern medicine and augment traditional pharmaceutics in a meaningful way. However, a key challenge to advancing NA therapies into the clinical setting and on to the market is the safe and effective delivery to the target tissue and cell. Lipid Nanoparticles (LNP) have been extensively investigated and are currently the most advanced vector for the delivery of NA drugs, as evidenced by the approval of Onpattro for treatment of Amyloidosis in the US and EU in 2018. This article provides a comprehensive review of the state-of-the-art for LNP technology. We discuss key advances in the design and development of LNP, leading to a broad range of therapeutic applications. Finally, the current status of this technology in clinical trials and its future prospects are discussed.
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http://dx.doi.org/10.1016/j.addr.2020.06.002 | DOI Listing |
Biomater Sci
January 2025
School of Chemistry, Chemical Engineering and Life Science, Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases, Wuhan University of Technology, 122 Luoshi Road, Wuhan 430070, China.
To enhance the antibacterial efficacy of tildipirosin against (S.A.) infections, optimized solid lipid nanoparticles loaded with tildipirosin (SLN-TD) were developed, using docosanoic acid (DA), octadecanoic acid (OA), hexadecanoic acid (HA), and tetradecanoic acid (TA) as lipid components.
View Article and Find Full Text PDFJ Control Release
January 2025
Bioprocessing Technology Institute (BTI), Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Republic of Singapore. Electronic address:
mRNA-loaded lipid nanoparticles (mRNA-LNPs) hold great potential for disease treatment and prevention. LNPs are normally made from four lipids including ionizable lipid, helper lipid, cholesterol, and PEGylated lipid (PEG-lipid). Although PEG-lipid has the lowest content, it plays a crucial role in the effective delivery of mRNA-LNPs.
View Article and Find Full Text PDFJ Control Release
January 2025
Department of Pharmaceutical Sciences, College of Pharmacy, Robertson Life Sciences Building, Oregon State University, Portland, OR 97201, USA; Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA; Department of Biomedical Engineering, Robertson Life Sciences Building, Oregon Health & Science University, Portland, OR 97201, USA. Electronic address:
Lipid nanoparticles (LNPs) have shown great potential in the field of gene therapy for retinal diseases. To expand on this application, we investigated LNP-mediated mRNA delivery to the anterior chamber of the eye via the intracameral (IC) route of administration. Here, we show that IC injections of LNPs facilitated protein expression and gene editing in the trabecular meshwork (TM).
View Article and Find Full Text PDFInt J Pharm
January 2025
Department of Pharmaceutics, Institute of Pharmaceutical Sciences, University of Freiburg, Sonnenstr. 5, Freiburg i. Br. 79104 Germany; ten23 health AG, Mattenstr. 22, Basel 4058 Switzerland. Electronic address:
Lipid nanoparticles (LNPs) have demonstrated their therapeutic potential as safe and effective drug delivery systems for nucleic acids during the COVID-19 pandemic. However, one of the main challenges during technical CMC (Chemistry, Manufacturing, and Controls) development is their long-term stability at temperatures of 2-8 °C or higher, which may be improved by the removal of water by lyophilization. In this study, we identified lyo-/cryo-protectants for freeze-dried mRNA-LNP formulations beyond conventional excipients such as sucrose and trehalose as T-modifiers using polyA as a surrogate.
View Article and Find Full Text PDFActa Biomater
January 2025
College of Chemistry, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, PR China. Electronic address:
mRNA-based protein replacement therapy has become one of the most widely applied forms of mRNA therapy, with lipid nanoparticles (LNPs) being extensively studied as efficient delivery platforms for mRNA. However, existing LNPs tend to accumulate in the liver or kidneys after intravenous injection, highlighting the need to develop vectors capable of targeting specific organs. In this study, we synthesized a small library of ionizable lipids and identified PPz-2R as a promising candidate, exhibiting lung-targeting capabilities, high mRNA transfection efficiency, and good stability through structure-activity relationship studies.
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