Background: Dietary flavonols may play an important role in the adjunct therapy of chronic inflammation. The availability of therapeutic formulations of pentahydroxyflavone glycoside, rutoside (RU), led us to investigate the ability of this molecule to modulate the release of various proinflammatory mediators from human activated macrophages in vitro and to ameliorate arthritic markers in a rat model. Methods: RU was added simultaneously to human macrophages during their activation. Cells were then analyzed for inflammation-related gene expression using a specific array, and cell supernatants were collected to measure inflammatory mediators. RU was also injected into adjuvant-induced arthritic rats, and disease progression and body weight were evaluated until 50 days after injection. Sera and peritoneal macrophages were also collected to quantify the RU effect on various inflammatory markers. Results: RU inhibited inflammation-related gene expression in activated human macrophages and the release of nitric oxide, tumor necrosis factor-alpha, interleukin (IL)-1, and IL-6 from these cells. In a rat model, RU inhibited clinical signs of chronic arthritis, correlating with decreased levels of inflammatory cytokines detected in rat sera and macrophage supernatants. Conclusion: Thus, RU may have clinical value in reducing inflammatory manifestations in human arthritis and other inflammatory diseases.

Antibiotic resistance has become a major issue in public health especially for one of the most used antibiotics; the third-generation cephalosporins. One of the main resistance mechanisms in Enterobacteriaceae, is the production of Extended-Spectrum β-lactamases. Here, we demonstrated that the oligonucleotide therapy is an efficient approach to reduce the resistance of bacteria to antibiotic treatment. Lipid oligonucleotides (LONs) were proved to be efficient strategies in both delivering the oligonucleotide sequences in the prokaryotic cells and decreasing the Minimum Inhibitory Concentration of resistant bacteria to a third generation cephalosporin, the ceftriaxone. Accordingly, we demonstrated the strong antimicrobial potential of this LON strategy targeting the ß-lactamase activity on both clinical and laboratory strains. Our results support the concept that the self-delivery of oligonucleotide sequences via lipid conjugation may be extended to other antimicrobial drugs, which opens novel ways to struggle against the antibiotic resistance.

One of the greatest challenges in the field of biofabrication remains the discovery of suitable bioinks that satisfy physicochemical and biological requirements. Despite recent advances in tissue engineering and biofabrication, progress has been limited to the development of technologies using polymer-based materials. Here, we show that a nucleotide lipid-based hydrogel resulting from the self-assembly of nucleotide lipids can be used as a bioink for soft tissue reconstruction using injection or extrusion-based systems. To the best of our knowledge, the use of a low molecular weight hydrogel as an alternative to polymeric bioinks is a novel concept in biofabrication and 3D bioprinting. Rheological studies revealed that nucleotide lipid-based hydrogels exhibit suitable mechanical properties for biofabrication and 3D bioprinting, including i) fast gelation kinetics in a cell culture medium and ii) shear moduli and thixotropy compatible with extruded oral cell survival (human gingival fibroblasts and stem cells from the apical papilla). This polymer-free soft material is a promising candidate for a new bioink design.

Pharmaceutical development and manufacturing process optimization work was undertaken in order to propose a potential paediatric rectal formulation of azithromycin as an alternative to existing oral or injectable formulations. The target product profile was to be easy-to-use, cheap and stable in tropical conditions, with bioavailability comparable to oral forms, rapidly achieving and maintaining bactericidal concentrations. PEG solid solution suppositories were characterized in vitro using visual, HPLC, DSC, FTIR and XRD analyses. In vitro drug release and in vivo bioavailability were assessed; a study in rabbits compared the bioavailability of the optimized solid solution suppository to rectal solution and intra-venous product (as reference) and to the previous, non-optimized formulation (suspended azithromycin suppository). The bioavailability of azithromycin administered as solid solution suppositories relative to intra-venous was 43%, which compared well to the target of 38% (oral product in humans). The results of 3-month preliminary stability and feasibility studies were consistent with industrial production scale-up. This product has potential both as a classical antibiotic and as a product for use in severely ill children in rural areas. Industrial partners for further development are being sought.