Evaluation of the effect of solid and cationic lipids on siRNA delivery systems
Citation:
Oner E, Kotmakci M, Debelec-Butuner B, Kantarci AG, Evaluation of the effect of solid and cationic lipids on siRNA delivery systems, BioTurkey International Biotechnology Congress, Istanbul, Turkey, March 5-7, 2020, 2020Download Item:
Abstract:
This study aims to develop nanoparticles with different types of solid and cationic
lipids and evaluate them as siRNA delivery systems. For this purpose, we prepared
a series of lipid nanoparticles by combining cationic lipids (DOTMA, stearylamine,
DDAB, and Esterquat-1) with solid lipids [Precirol ATO 5 (P), Compritol 888 ATO
(C), Cetyl palmitate 15 (CP15)] by a modified hot microemulsion method. The
developed cationic solid lipid nanoparticles (cSLNs) were characterized in terms of
particle size, size distribution, and zeta potential using a Malvern NanoZS
Instrument. After determining the complexation ability of cSLNs with siRNA, the
Resazurin assay was conducted to evaluate and compare their cytotoxicity. The
cSLNs which successfully bind siRNA and show low cytotoxicity were further
investigated by in vitro cellular uptake (fluorescence microscopy) and gene silencing
(Western Blot) studies. According to characterization measurements, all
formulations had a small particle size (< 200 nm), narrow size distribution
(polydispersity index, PDI< 0.5), and high positive zeta potential (> +25 mV). The
cSLN with Esterquat-1 was eliminated from further studies due to the poor
complexation capacity. The use of cSLN with stearylamine was found inappropriate
because of its high toxicity on both DU145 and PC-3 prostate cancer cells. None of
these formulations showed effective gene silencing on DU145 cells. Only cSLN
including P:C mixture with DDAB or DOTMA were uptaken by PC-3 cells and
showed silencing efficiency. This study shows the importance of the lipid type
selection for siRNA delivery systems and how this changes the transfection
efficiency of these systems.
Author's Homepage:
http://people.tcd.ie/onere
Author: Oner-Bozkurt, Ezgi
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BioTurkey International Biotechnology CongressCollections
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Full text availableKeywords:
Cationic solid lipid nanoparticles, cytotoxicity, gene delivery systems, RNA interference, siRNA, transfection efficiencySubject (TCD):
Cancer , Genes & Society , Nanoscience & Materials , CANCER , Drug Delivery Systems , Gene therapy , Nano Biotechnology , NanoMedicine , Prostate cancerMetadata
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