Efficacy increase of lipid nanoparticles in vivo by inclusion of bis(monoacylglycerol)phosphate

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 . The nanoparticles were prepared from ionizable lipid, 1,2-distearoyl- -glycerol-3-phosphocholine, cholesterol, 1,2-di...

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Published inNanomedicine (London, England) Vol. 17; no. 20; pp. 1399 - 1410
Main Authors Sagi, Amit, Mukthavaram, Rajesh, Recatto, River, Hong, Hyojung, Davis, Michael, Trelles, Ramon Diaz, El-Mecharrafie, Nadja, Acharya, Grishma, Gomez, Abraham, Leu, Angel, Tachikawa, Kiyoshi, Sacchetti, Cristiano, Soontornniyomkij, Benchawanna, Rajappan, Kumar, Karmali, Priya, Chivakula, Padmanabh
Format Journal Article
LanguageEnglish
Published England 01.08.2022
Subjects
Humans
Monoglycerides - metabolism
Nanoparticles - chemistry
Phosphates
RNA, Messenger
gene delivery
lipid nanoparticles
mRNA therapy
protein expression
bis(monoacylglycerol) phosphate
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Summary: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 . The nanoparticles were prepared from ionizable lipid, 1,2-distearoyl- -glycerol-3-phosphocholine, cholesterol, 1,2-dimyristoyl- -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 and . Lipid nanoparticles composed of BMP displayed increased endosomal membrane fusion and improved mRNA delivery to the cytosol. The results establish the foundation for future development of these nanoparticulated entities by designing new BMP derivatives and correlating structures to enhanced pharmacokinetic profiles.
ISSN:1743-5889
1748-6963
DOI:10.2217/nnm-2022-0002