Mucoactive drugs and multiple applications in pulmonary disease therapy.

Mucus is a complex polymeric hydrogel that serves as a critical defense in several organs. In the lungs, it provides a formidable barrier against inhaled particles such as microorganisms. In addition, mucus is essential for normal lung physiology, as it promotes immune tolerance and facilitates a normal commensal pulmonary microbiome.

Gene transfection using branched cationic amphiphilic compounds for an aerosol administration in cystic fibrosis context.

For cystic fibrosis gene therapy, the aerosolization of genetic materials is the most relevant delivery strategy to reach the airway epithelium. However, aerosolized formulations have to resist shear forces while maintaining the integrity of plasmid DNA (pDNA) during its journey from the nebulization to the epithelial cells. Herein, we compared the efficiency of gene delivery by aerosolization of two types of formulations: (i) BSV163, a branched cationic amphiphilic compound, co-formulated with different DOPE ratios (mol/mol) and DMPE-PEG5000 and (ii) 25 KDa branched polyethylenimine (b-PEI)-based formulation used as control.

Apparent Yield Stress of Sputum as a Relevant Biomarker in Cystic Fibrosis.

The mucus obstructing the airways of Cystic Fibrosis (CF) patients is a yield stress fluid. Linear and non-linear rheological analyses of CF sputa can provide relevant biophysical markers, which could be used for the management of this disease. Sputa were collected from CF patients either without any induction or following an aerosol treatment with the recombinant human DNAse (rhDNAse, Pulmozyme).

Optimizations of In Vitro Mucus and Cell Culture Models to Better Predict In Vivo Gene Transfer in Pathological Lung Respiratory Airways: Cystic Fibrosis as an Example.

The respiratory epithelium can be affected by many diseases that could be treated using aerosol gene therapy. Among these, cystic fibrosis (CF) is a lethal inherited disease characterized by airways complications, which determine the life expectancy and the effectiveness of aerosolized treatments. Beside evaluations performed under in vivo settings, cell culture models mimicking in vivo pathophysiological conditions can provide complementary insights into the potential of gene transfer strategies.

Antibacterial and transfection activities of nebulized formulations incorporating long n-alkyl chain silver N-heterocyclic carbene complexes.

The development of new antibacterial molecules is essential in view of the emergence of pathogenic strains resistant to multiple antibiotics. Among the infectious pathologies, pulmonary infections are particularly difficult to treat due to the complexity of lung anatomy and the presence of natural barriers such as mucus. At present, the aerosol delivery of antibacterial compounds is still poorly employed.

Antibacterial effect and DNA delivery using a combination of an arsonium-containing lipophosphoramide with an N-heterocyclic carbene-silver complex - Potential benefits for cystic fibrosis lung gene therapy.

Cystic Fibrosis (CF), the most common chronic genetic disorder among the Caucasian population, is a life-threatening disease mainly due to respiratory failures resulting from chronic infections and inflammation. Although research in the pharmacological field has recently made significant progress, gene therapy still remains a promising strategy to cure CF, especially because it should be applicable to any patient whatever the mutation profile. Until now, little attention has been paid to bacterial lung infections with regard to gene delivery to the airways; yet, this could greatly impact on the success of gene therapy.

Enhancement of lung gene delivery after aerosol: a new strategy using non-viral complexes with antibacterial properties.

The pathophysiology of obstructive pulmonary diseases, such as cystic fibrosis (CF), leads to the development of chronic infections in the respiratory tract. Thus, the symptomatic management of the disease requires, in particular, repetitive antibiotherapy. Besides these antibacterial treatments, certain pathologies, such as CF or chronic obstructive pulmonary disease (COPD), require the intake of many drugs.

Highly efficient SiRNA and gene transfer into hepatocyte-like HepaRG cells and primary human hepatocytes: new means for drug metabolism and toxicity studies.

The metabolically competent hepatocyte-like human HepaRG cells represent a suitable alternative in vitro cell model to human primary hepatocytes. Here, we describe the culture procedure required to expand progenitor HepaRG cells and to differentiate them into hepatocyte-like cells. Transient transfection of gene and siRNA into cultured cells, using nonviral strategies, is an invaluable technique to decipher gene functions.

New functional degradable and bio-compatible nanoparticles based on poly(malic acid) derivatives for site-specific anti-cancer drug delivery.

Design of an efficient site-specific drug delivery system based on degradable functional polymers still remains challenging. In this work, we synthesized and characterized three degradable functional polyesters belonging to the poly(malic acid) family: the poly(benzyl malate) (PMLABe), the poly(ethylene glycol)-b-poly(benzyl malate) (PEG(42)-b-PMLABe), the biotin-poly(ethylene glycol)-b-poly(benzyl malate) (Biot-PEG(62)-PMLABe). Starting from these building blocks, we were able to prepare the corresponding well-defined degradable functional nanoparticles whose toxicity was evaluated in vitro on normal and cancer cell lines.

Preferential induction of the AhR gene battery in HepaRG cells after a single or repeated exposure to heterocyclic aromatic amines.

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) are two of the most common heterocyclic aromatic amines (HAA) produced during cooking of meat, fish and poultry. Both HAA produce different tumor profiles in rodents and are suspected to be carcinogenic in humans. In order to better understand the molecular basis of HAA toxicity, we have analyzed gene expression profiles in the metabolically competent human HepaRG cells using pangenomic oligonucleotide microarrays, after either a single (24-h) or a repeated (28-day) exposure to 10 μM PhIP or MeIQx.

Highly efficient gene transfer into hepatocyte-like HepaRG cells: new means for drug metabolism and toxicity studies.

HepaRG progenitor cells are capable of differentiating into hepatocyte-like cells that express a large set of liver-specific functions. These cells, however, only express small amounts of an important cytochrome P450, the CYP2E1, which limits their use for toxicological studies of drugs metabolized by this pathway. Our aim was to establish an efficient transfection protocol to increase CYP2E1 expression in HepaRG cells.

The double odyssey of Madagascan polystome flatworms leads to new insights on the origins of their amphibian hosts.

Polystomatid flatworms are parasites of high host specificity, which mainly infect amphibian hosts. Only one polystome species has so far been recorded from Madagascar despite the high species richness and endemicity of amphibians on this island. Out of the 86 screened Malagasy frog species, we recovered polystomes from 25 in the families Ptychadenidae and Mantellidae.

pEg6, a spire family member, is a maternal gene encoding a vegetally localized mRNA in Xenopus embryos.

Background Information: In Xenopus, during oocyte maturation and the segmentation period, cell cycle progression is independent of new transcription, but requires de novo translation. This suggests that the completion of oocyte maturation and then the rapid cell division period is controlled exclusively at a post-transcriptional level by specific gene products. To isolate these maternal genes, a differential screening of a Xenopus egg cDNA library was performed.