Navigating the intricate in-vivo journey of lipid nanoparticles tailored for the targeted delivery of RNA therapeutics: a quality-by-design approach
Abstract RNA therapeutics, such as mRNA, siRNA, and CRISPR–Cas9, present exciting avenues for treating diverse diseases. However, their potential is commonly hindered by vulnerability to degradation and poor cellular uptake, requiring effective delivery systems. Lipid nanoparticles (LNPs) have emerg...
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| Format: | Article |
| Language: | English |
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BMC
2024-11-01
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| Series: | Journal of Nanobiotechnology |
| Online Access: | https://doi.org/10.1186/s12951-024-02972-w |
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| author | Elahe Haghighi Samira Sadat Abolmaali Ali Dehshahri Seyed Ali Mousavi Shaegh Negar Azarpira Ali Mohammad Tamaddon |
| author_facet | Elahe Haghighi Samira Sadat Abolmaali Ali Dehshahri Seyed Ali Mousavi Shaegh Negar Azarpira Ali Mohammad Tamaddon |
| author_sort | Elahe Haghighi |
| collection | DOAJ |
| description | Abstract RNA therapeutics, such as mRNA, siRNA, and CRISPR–Cas9, present exciting avenues for treating diverse diseases. However, their potential is commonly hindered by vulnerability to degradation and poor cellular uptake, requiring effective delivery systems. Lipid nanoparticles (LNPs) have emerged as a leading choice for in vivo RNA delivery, offering protection against degradation, enhanced cellular uptake, and facilitation of endosomal escape. However, LNPs encounter numerous challenges for targeted RNA delivery in vivo, demanding advanced particle engineering, surface functionalization with targeting ligands, and a profound comprehension of the biological milieu in which they function. This review explores the structural and physicochemical characteristics of LNPs, in-vivo fate, and customization for RNA therapeutics. We highlight the quality-by-design (QbD) approach for targeted delivery beyond the liver, focusing on biodistribution, immunogenicity, and toxicity. In addition, we explored the current challenges and strategies associated with LNPs for in-vivo RNA delivery, such as ensuring repeated-dose efficacy, safety, and tissue-specific gene delivery. Furthermore, we provide insights into the current clinical applications in various classes of diseases and finally prospects of LNPs in RNA therapeutics. Graphical Abstract |
| format | Article |
| id | doaj-art-9f99a8d8483e494a878a3b8527dd2094 |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-9f99a8d8483e494a878a3b8527dd20942024-11-17T12:46:58ZengBMCJournal of Nanobiotechnology1477-31552024-11-0122115510.1186/s12951-024-02972-wNavigating the intricate in-vivo journey of lipid nanoparticles tailored for the targeted delivery of RNA therapeutics: a quality-by-design approachElahe Haghighi0Samira Sadat Abolmaali1Ali Dehshahri2Seyed Ali Mousavi Shaegh3Negar Azarpira4Ali Mohammad Tamaddon5Department of Pharmaceutical Nanotechnology, Shiraz University of Medical SciencesDepartment of Pharmaceutical Nanotechnology, Shiraz University of Medical SciencesCenter for Nanotechnology in Drug Delivery, Shiraz University of Medical SciencesLaboratory of Microfluidics and Medical Microsystems, Research Institute for Medical Sciences, Mashhad University of Medical SciencesStem Cells Technology Research Center, Shiraz University of Medical SciencesDepartment of Pharmaceutical Nanotechnology, Shiraz University of Medical SciencesAbstract RNA therapeutics, such as mRNA, siRNA, and CRISPR–Cas9, present exciting avenues for treating diverse diseases. However, their potential is commonly hindered by vulnerability to degradation and poor cellular uptake, requiring effective delivery systems. Lipid nanoparticles (LNPs) have emerged as a leading choice for in vivo RNA delivery, offering protection against degradation, enhanced cellular uptake, and facilitation of endosomal escape. However, LNPs encounter numerous challenges for targeted RNA delivery in vivo, demanding advanced particle engineering, surface functionalization with targeting ligands, and a profound comprehension of the biological milieu in which they function. This review explores the structural and physicochemical characteristics of LNPs, in-vivo fate, and customization for RNA therapeutics. We highlight the quality-by-design (QbD) approach for targeted delivery beyond the liver, focusing on biodistribution, immunogenicity, and toxicity. In addition, we explored the current challenges and strategies associated with LNPs for in-vivo RNA delivery, such as ensuring repeated-dose efficacy, safety, and tissue-specific gene delivery. Furthermore, we provide insights into the current clinical applications in various classes of diseases and finally prospects of LNPs in RNA therapeutics. Graphical Abstracthttps://doi.org/10.1186/s12951-024-02972-w |
| spellingShingle | Elahe Haghighi Samira Sadat Abolmaali Ali Dehshahri Seyed Ali Mousavi Shaegh Negar Azarpira Ali Mohammad Tamaddon Navigating the intricate in-vivo journey of lipid nanoparticles tailored for the targeted delivery of RNA therapeutics: a quality-by-design approach Journal of Nanobiotechnology |
| title | Navigating the intricate in-vivo journey of lipid nanoparticles tailored for the targeted delivery of RNA therapeutics: a quality-by-design approach |
| title_full | Navigating the intricate in-vivo journey of lipid nanoparticles tailored for the targeted delivery of RNA therapeutics: a quality-by-design approach |
| title_fullStr | Navigating the intricate in-vivo journey of lipid nanoparticles tailored for the targeted delivery of RNA therapeutics: a quality-by-design approach |
| title_full_unstemmed | Navigating the intricate in-vivo journey of lipid nanoparticles tailored for the targeted delivery of RNA therapeutics: a quality-by-design approach |
| title_short | Navigating the intricate in-vivo journey of lipid nanoparticles tailored for the targeted delivery of RNA therapeutics: a quality-by-design approach |
| title_sort | navigating the intricate in vivo journey of lipid nanoparticles tailored for the targeted delivery of rna therapeutics a quality by design approach |
| url | https://doi.org/10.1186/s12951-024-02972-w |
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