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Optimization of miRNA delivery by using a polymeric conjugate based on deoxycholic acid-modified polyethylenimine

Published on Jun 1, 2019in International Journal of Pharmaceutics4.213
· DOI :10.1016/j.ijpharm.2019.05.009
Fatemeh Radmanesh (Shahid Beheshti University of Medical Sciences and Health Services), Hamid Sadeghi Abandansari9
Estimated H-index: 9
(Royan Institute)
+ 5 AuthorsHossein Baharvand44
Estimated H-index: 44
(University of Science and Culture)
Abstract
Abstract Safe and efficient delivery of microRNA (miRNA) molecules is essential for their successful transition from research to the clinic setting. In the present study, we have used a bile acid, deoxycholic acid (DA), to modify 1.8 kDa branched polyethylenimine (bPEI1.8) and subsequently investigated gene delivery features of the resultant conjugates (PEI-DAn). We found significant differences between the PEI-DAn conjugates and conventional bPEIs with respect to miRNA condensation ability, buffering capacity, cellular uptake, and intracellular gene release behavior in endothelial cells (ECs) isolated from human umbilical vein (HUVECs). Changes in the conjugation degree greatly influenced the transfection performance of the PEI-DAn conjugates with respect to miRNA condensation and decondensation properties as well as cellular uptake behavior. The PEI-DA3 conjugates could significantly enhance the expression level of miRNA-210 in HUVECs. The overexpressed miRNA-210, in turn, markedly downregulated the expression levels of Efna3 and Ptp1b as well as led to a substantial rise in HUVECs' migration rate in a wound healing assay. Collectively, our results have demonstrated that PEI-DA3 conjugates facilitate the formation of stable nanocomplexes that are loose enough to release miRNAs into the cytosol. The free bioavailable miRNAs, in turn, result in efficient gene silencing comparable to bPEI25 as well as Lipofectamine RNAiMAX.
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