New insights and advances on pyomelanin production: from microbial synthesis to applications

International audiencePyomelanin is a brown-black phenolic polymer and results from the oxidation of homogentisic acid (HGA) in the L-tyrosine pathway. As part of the research for natural and active ingredients issued from realistic bioprocesses, this work re-evaluates the HGA pigment and makes an updated inventory of its syntheses, microbial pathways, and properties, with tracks and recent advances for its large-scale production. The mechanism of the HGA polymerization is also well documented. In alkaptonuria, pyomelanin formation leads to connective tissue damage and arthritis, most probably due to the ROS issued from HGA oxidation. While UV radiation on human melanin may generate degradation products, pyomelanin is not photodegradable, is hyperthermostable, and has other properties better than L-Dopa melanin. This review aims to raise awareness about the potential of this pigment for various applications, not only for skin coloring and protection but also for other cells, materials, and as a promising (semi)conductor for bioelectronics and energy

Interactions and antioxidant stability of sesamol in dry-emulsions: Interactions and antioxidant stability

International audienceDry emulsions prepared from saccharose (SAC),Labrafil M 1944 CS, sesamol (SEOH), and hydroxypropylmethylcellulose(HPMC) or sodium caseinate (SC)by grinding or dissolution, and different desiccation techniques(spray (SD)- or freeze (FD)-drying, or heating at60 C) were investigated to determine possible interactionsbetween mixture components. The goal of this study was todetermine the best formulation which will regenerate perfectly,after water dilution of dry emulsions, the initial liquidemulsion with the same characteristics that before drying.The morphological state of SAC and dry emulsions weredetermined by scanning electron microscopy analysis (SEM)analysis. Glass transition temperature, and melting (endothermic),decomposition (endothermic), oxidation (exothermic)peak temperatures and enthalpies were measured bydifferential scanning calorimetry (DSC). The antioxidantactivity of emulsions was evaluated through their ability toreduce 1,1-diphenyl-2-picrylhydrazil (DPPH) free radical.SEM analysis showed that SD-prepared, SC-containing dryemulsions formed better spherical particles with smoothsurface at about 5 lm diameter as compared to emulsioncontaining HPMC. These former emulsions also showedmore thermal stability by DSC. The combined results of thethree analytical techniques emphasized the importance of thedry emulsion process regarding the efficiency and the thermalstability of antioxidant substances. A specific physicaland/or chemical combination (such as hydrogen bond) sufficientlystable, at about 150 C, could be suggested when thetechnique used for dry emulsion preparation was SD. Afterwater dilution, this dry emulsion obtained from quaternarymixture: SAC, Labrafil, SEOH and SC, will regenerate theinitial liquid emulsion with the same characteristics thatbefore drying

Docetaxel-trastuzumab stealth immunoliposome: development and in vitro proof of concept studies in breast cancer

Background: Trastuzumab plus docetaxel is a mainstay to treat HER2-positive breast cancers. However, developing nanoparticles could help to improve the efficacy/toxicity balance of this doublet by improving drug trafficking and delivery to tumors. This project aimed to develop an immunoliposome in breast cancer, combining docetaxel encapsulated in a stealth liposome engrafted with trastuzumab, and comparing its performances on human breast cancer cell lines with standard combination of docetaxel plus trastuzumab. Methods: Several strategies to engraft trastuzumab to pegylated liposomes were tested. Immunoliposomes made of natural (antibody nanoconjugate-1 [ANC-1]) and synthetic lipids (ANC-2) were synthesized using standard thin film method and compared in size, morphology, docetaxel encapsulation, trastuzumab engraftment rates and stability. Antiproliferative activity was tested on human breast cancer models ranging from almost negative (MDA-MB-231), positive (MDA-MB-453) to overexpressing (SKBR3) HER2. Finally, cell uptake of ANC-1 was studied by electronic microscopy. Results: ANC-1 showed a greater docetaxel encapsulation rate (73%+/- 6% vs 53%+/- 4%) and longer stability (up to 1 week) as compared with ANC-2. Both ANC presented particle size <= 150 nm and showed similar or higher in vitro antiproliferative activities than standard treatment, ANC-1 performing better than ANC-2. The IC50s, for docetaxel combined to free trastuzumab were 8.7 +/- 4, 2 +/- 0.7 and 6 +/- 2 nM with M DA-MB-231, M DA-M B-453 and SKBR3, respectively. The IC50s for ANC-1 were 2.5 +/- 1, 1.8 +/- 0.6 and 3.4 +/- 0.8 nM and for ANC-2 were 1.8 +/- 0.3 nM, 2.8 +/- 0.8 nM and 6.8 +/- 1.8 nM with MDA-MB-231, MDA-MB-453 and SKBR3, respectively. Cellular uptake appeared to depend on HER2 expression, the higher the expression, the higher the uptake. Conclusion: In vitro results suggest that higher antiproliferative efficacy and efficient drug delivery can be achieved in breast cancer models using nanoparticles