DODMA

Micrometer-sized porous honeycomb-patterned thin films based on hybrid complexes formed via electrostatic interaction between Mn(III) meso-tetra(4-sulfonatophenyl) porphine chloride (an acid form, {MnTPPS}) and dimethyldioctadecylammonium bromide (DODMABr). The morphology of the microporous thin films can be well regulated by controlling the concentration of MnTPPS-DODMA complexes, DODMABr, and polystyrene (PS), respectively. The formation of the microporous thin films was largely influenced by different solvents. The well-ordered microporous films of MnTPPS-DODMA complexes exhibit a more efficient antibacterial activity under visible light than those of hybrid complexes of nanoparticles modified with DODMABr, implying that well-ordered microporous films containing porphyrin composition can improve photochemical activity and more dominance in applications in biological medicine fields.

Illuminating the factors that influence the organic carbon content normalized sorption coefficient (K(oc)) of organoclays towards hydrophobic organic compounds (HOCs) is meaningful for predicting and optimizing the sorption capacity of organoclay. In this paper, the structures and sorption characteristics towards HOCs of organobentonites synthesized with octadecyltrimethylammonium chloride (OTMAC) and dioctadecyldimethylammonium chloride (DODMAC) were studied in order to further account for the variation of K(oc). The conformations of bentonite-sorbed OTMA(+) and DODMA(+) transformed from disorder to order as surfactant loading increasing. The packing densities of DODMA(+) aggregates were higher than those of OTMA(+) aggregates at low surfactant loadings. At high surfactant loading region (1.0-1.4CEC for OTMA-Bent and 0.5-0.7CEC for DODMA-Bent), similar paraffin-type bilayer arrangements were adopted by sorbed OTMA(+) and DODMA(+), and their packing densities were close under the same f(oc) in dry state organobentonites. It was found that loading forms of surfactant onto bentonite had important effect on the structure of organobentonite in water-saturated state, and further to influence the sorption characteristics of organobentonite towards HOCs. When the loading exceeded 0.8CEC, OTMAC in salt molecule form appeared in the clay interlayer via hydrophobic interaction. The strong hydration of surfactant ammonium heads and the counterions (Cl(-)) in aqueous system interfered the hydrophobic interaction of the OTMA(+) clusters and destroyed the close packing in clay galleries. As a result, the sorption capacity of organobentonite towards HOCs was sharply reduced.

Purpose:Understanding mechanisms of cellular uptake and intracellular release would enable better design of nanocarriers for delivery of nucleic acids such as siRNA and microRNA (miRNA).Method:In this study, we investigated cellular pharmacokinetics of siRNA by co-encapsulating fluorescently labeled siRNA and molecular beacon (MB) in four different formulations of cationic lipid nanoparticles (LNPs). A miRNA mimic was also used as a probe for investigating cellular pharmacokinetics, which correlated well with RNAi activities.Results:We tried to find the best LNP formulation based on the combination of DOTMA and DODMA. When the DOTMA/DODMA ratio was at 5/40, the LNP containing a luciferase siRNA produced the highest gene silencing activity. The superior potency of DOTMA/DODMA could be attributed to higher uptake and improved ability to facilitate siRNA release from endosomes subsequent to uptake.Conclusions:Our findings may provide new insights into RNAi transfection pathways and have implications on cationic LNP design.

MicroRNA185 (miR185), an endogenous noncoding RNA with 23 nucleotides, is one of key posttranscriptional modulators of cholesterol metabolism in hepatic cells. The antisense inhibitor of miR185 (miR185i) could decrease cholesterol level in vivo, providing a promising agent for anti-atherosclerosis strategy. In this work, a novel LipomiR185i was constructed by thin film hydration method and post-PEGylation as DOPE: DOTAP: Chol: DSPE-PEG2000at the molar ratio of 1:1:1:0.1 with a nitrogen-to-phosphate ratio of 3, through the optimization of three cationic lipids (DOTAP, DODMA and DLin-MC3-DMA), six helper lipids (PC-98T, HSPC, DOPE, DMPC, DPPC and DSPC), different amounts and incorporation approaches of DSPE-PEG2000and nitrogen-to-phosphate ratio. LipomiR185i was characterized with a particle size of 174 ± 11 nm, a zeta potential of 7.0 ± 3.3 mV, high encapsulation efficiency and transfection activity. It could protect miR185i from the rapid degradation by nucleases in serum, enhance cellular uptake and promote lysosomal escape in HepG2 cells. LipomiR185i could accumulate in the liver and remain for at least two weeks. More importantly, LipomiR185i significantly down-regulated the hepatic endogenous miR185 level in vitro and in vivo without significant tissue damage at 14 mg⋅kg-1. The construction of LipomiR185i provides a potential anti-atherosclerotic nanodrug as well as a platform for delivering small RNAs to the liver efficiently and safely.