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• W4225566822 abstract "Purpose Polylipoic acid-based nanoparticles ([email protected]) have a great potential as nanovectors, and may represent a future potential therapeutic tool for delivering active molecules to different organs in complex diseases. However, their tissue distribution, accumulation, persistence and clearance in vivo are not known yet, as well as specific cellular penetration and ability to deliver subgenomic particles to the intracellular space. We have investigated it in vitro and in vivo in heart, kidney and in splancnic organs of healthy rodents. Methods Healthy Sprague-Dawley rats were injected with 10mg/Kg of [email protected] NPs rhodamine conjugated via tail vein and compared with 7 controls. Rats were sacrificed at different time points from 10 minutes to 2 months after NPs injection. NPs fluorescence and MFI rate in whole collected organs and in the different cell types have been measured using an “image analysis quantification algorithm” software of confocal microscope Results NPs fluorescence was identified immediately after injection in the heart and later on into splanchnic organs. After 3 hours, the heart was able to retain an amount of NPs 2-fold higher than that observed in the liver (30.63±10.78MFI vs 13.93±1.42MFI) and about 5-times higher than lungs and spleen and three time higher than kidney. The heart showed the maximal NPs accumulation (3.69MFI/h) compared to all the other organs such as kidney (0.465MFI/h at 3h), liver (0.2MFI at 3days) and spleen (1.06MFI at 1h). Myocytes showed 25.06±5.13MFI/cell at 3 hours with a clearance rate of -0.4MFI/h/cell while kidney tubular cells showed their maximal accumulation rate at 3days with 19.14±3.148MFI/cell. Liver, instead, revealed a different kinetic between hepatocytes and kupffer cells (18.94±3.03 vs 37.64±19.14MFI at 1day respectively). No organ damage and histopathological lesions were observed after NPs injection. In vitro studies showed the ability of NPs to vehiculate miRNAs to intracellular cardiomyocytes. Conclusion his new approach constitutes a biological minimally invasive and safe method to deliver active molecules to target organs and cells such as heart and kidney Polylipoic acid-based nanoparticles ([email protected]) have a great potential as nanovectors, and may represent a future potential therapeutic tool for delivering active molecules to different organs in complex diseases. However, their tissue distribution, accumulation, persistence and clearance in vivo are not known yet, as well as specific cellular penetration and ability to deliver subgenomic particles to the intracellular space. We have investigated it in vitro and in vivo in heart, kidney and in splancnic organs of healthy rodents. Healthy Sprague-Dawley rats were injected with 10mg/Kg of [email protected] NPs rhodamine conjugated via tail vein and compared with 7 controls. Rats were sacrificed at different time points from 10 minutes to 2 months after NPs injection. NPs fluorescence and MFI rate in whole collected organs and in the different cell types have been measured using an “image analysis quantification algorithm” software of confocal microscope NPs fluorescence was identified immediately after injection in the heart and later on into splanchnic organs. After 3 hours, the heart was able to retain an amount of NPs 2-fold higher than that observed in the liver (30.63±10.78MFI vs 13.93±1.42MFI) and about 5-times higher than lungs and spleen and three time higher than kidney. The heart showed the maximal NPs accumulation (3.69MFI/h) compared to all the other organs such as kidney (0.465MFI/h at 3h), liver (0.2MFI at 3days) and spleen (1.06MFI at 1h). Myocytes showed 25.06±5.13MFI/cell at 3 hours with a clearance rate of -0.4MFI/h/cell while kidney tubular cells showed their maximal accumulation rate at 3days with 19.14±3.148MFI/cell. Liver, instead, revealed a different kinetic between hepatocytes and kupffer cells (18.94±3.03 vs 37.64±19.14MFI at 1day respectively). No organ damage and histopathological lesions were observed after NPs injection. In vitro studies showed the ability of NPs to vehiculate miRNAs to intracellular cardiomyocytes. his new approach constitutes a biological minimally invasive and safe method to deliver active molecules to target organs and cells such as heart and kidney" @default.
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• W4225566822 date "2022-04-01" @default.
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• W4225566822 title "Lipoic Acid F127@lpp Nanoparticles as a New Therapeutic Tool for Delivering Active Molecules" @default.
• W4225566822 doi "https://doi.org/10.1016/j.healun.2022.01.1257" @default.
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