Evaluation of New Fluorescent Lipophosphoramidates for Gene Transfer and Biodistribution Studies after Systemic Administration

Abstract

The objective of lung gene therapy is to reach the respiratory epithelial cells in order to deliver a functional nucleic acid sequence. To improve the synthetic carrier’s efficacy, knowledge of their biodistribution and elimination pathways, as well as cellular barriers faced, depending on the administration route, is necessary. Indeed, the in vivo fate guides the adaptation of their chemical structure and formulation to increase their transfection capacity while maintaining their tolerance. With this goal, lipidic fluorescent probes were synthesized and formulated with cationic lipophosphoramidate KLN47 (KLN: Karine Le Ny). We found that such formulations present constant compaction properties and similar transfection results without inducing additional cytotoxicity. Next, biodistribution profiles of pegylated and unpegylated lipoplexes were compared after systemic injection in mice. Pegylation of complexes led to a prolonged circulation in the bloodstream, whereas their in vivo bioluminescent expression profiles were similar. Moreover, systemic administration of pegylated lipoplexes resulted in a transient liver toxicity. These results indicate that these new fluorescent compounds could be added into lipoplexes in small amounts without perturbing the transfection capacities of the formulations. Such additional properties allow exploration of the in vivo biodistribution profiles of synthetic carriers as well as the expression intensity of the reporter gene.

Antimicrobial dependence of silver nanoparticles on surface plasmon resonance bands against <em>Escherichia coli</em>

“…Zhang et al39 reported that during the formation of AgNPs in the solution, there is biodegradation of HCHO to HCOO − via silver oxidation catalytic activity 40,41…”

Hepatic toxicity assessment of cationic liposome exposure in healthy and chronic alcohol fed mice

“…It has been demonstrated that the liver also has significance with regards to nano-sized material accumulation and toxicity as it has been shown to preferentially accumulate large quantities of these NMs following intravenous (IV) exposure compared to other organs ( Geraets et al, 2014 ; Kermanizadeh et al, 2015 ; Lipka et al, 2010 ; Sadauskas et al, 2009 ) and alongside the kidneys might be responsible for the clearance of NMs from the blood ( Geiser and Kreyling, 2010 ; Semmler-Behnke et al, 2008 ). Similar to other NMs, the IV administration of non-functionalised liposomes also results in large quantities of the materials accumulating in the liver ( Belmadi et al, 2016 ; Dicheva et al, 2016 ; Knudsen et al, 2014a ). It is understood that global alcohol abuse was the seventh leading cause of death in 2015, with 5.2% of the mortality worldwide attributed to consumption of alcoholic beverages ( Fulman et al, 2017 ).…”

Gut Flora-Mediated Metabolic Health, the Risk Produced by Dietary Exposure to Acetamiprid and Tebuconazole

“…The concentration changes in serum protein were slighter in the exposure than those in aminotransferase. The evaluation results revealed that liver was slightly impaired and mild dysfunction may have occurred in the exposure [ 13 ]. Moreover, these abnormalities were all found in different exposure groups, while no obvious joint effects were obtained in the combination exposure group.…”