Efficacy increase of lipid nanoparticles in vivo by inclusion of bis(monoacylglycerol)phosphate
| Autor: | Amit Sagi, Rajesh Mukthavaram, River Recatto, Hyojung Hong, Michael Davis, Ramon Diaz Trelles, Nadja El-Mecharrafie, Grishma Acharya, Abraham Gomez, Angel Leu, Kiyoshi Tachikawa, Cristiano Sacchetti, Benchawanna Soontornniyomkij, Kumar Rajappan, Priya Karmali, Padmanabh Chivakula |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Nanomedicine. 17:1399-1410 |
| ISSN: | 1748-6963 1743-5889 |
| DOI: | 10.2217/nnm-2022-0002 |
| Popis: | Aim: To investigate the effect of incorporating bis(monoacylglycerol)phosphate (BMP) lipid into a lipid nanoparticle and the functional transport of mRNA by the formulated nanoparticles in vivo. Materials & methods: The nanoparticles were prepared from ionizable lipid, 1,2-distearoyl- sn-glycerol-3-phosphocholine, cholesterol, 1,2-dimyristoyl- sn-glycerol PEG 2000, BMP and formulated mRNA encoding human erythropoietin. We measured the effect of BMP on physicochemical properties and impact on functional efficacy to transport mRNA to its target cells/tissue as measured by protein expression both in vitro and in vivo. Results: Lipid nanoparticles composed of BMP displayed increased endosomal membrane fusion and improved mRNA delivery to the cytosol. Conclusion: The results establish the foundation for future development of these nanoparticulated entities by designing new BMP derivatives and correlating structures to enhanced pharmacokinetic profiles. |
| Databáze: | OpenAIRE |
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