omega-Hydrazino linear polyethylenimine: a monoconjugation building block for nucleic acid delivery

Nonviral gene therapy requires efficient vectors that are able to deliver nucleic acids inside the targeted cell nucleus. Developing new tools for the synthesis of supramolecular vectors with improved transfection efficiency and better biodistribution is therefore a crucial issue. Here we describe the synthesis of a 140-mer linear polyethylenimine (L-PEI) terminated at one end by a highly nucleophilic hydrazine residue. This cationic polymer, whose backbone is well known for its remarkable gene-delivery efficiency, constitutes a building block for omega-regioselective conjugation to molecules through the formation of stable linkages such as the hydrazone bonds. To demonstrate the potential of the omega-hydrazino linear polyethylenimine, human serum transferrin, a ligand that is well know to improve gene-delivery systems, was used as a model of sensitive material. The blood protein was oxidized to generate an aldehyde function and was subsequently conjugated to hydrazino PEI. The new polyethylenimine-transferrin (PEI-Tf) vector was purified and was shown to condense plasmid DNA into compact superstructures compatible with cellular uptake. Finally, the cellular-binding and gene-delivery properties of PEI/DNA polyplexes incorporating different quantities of transferrin were evaluated by FACS analysis and luciferase assay.     

Poly(lactic acid)/low‐density polyethylene blends and its nanocomposites based on sepiolite

Poly(lactic acid) (PLA) nanocomposite ternary blends based on unmodified sepiolite were prepared by melt blending using a corotating twin‐screw extruder. Two grafted polymers were used as compatibilizer agents, in an effort to increase the PLA tensile toughness. The influence of incorporating a low‐cost commodity low‐density polyethylene, as dispersed phase to the composites on thermal degradation, and rheological and tensile properties was studied. The morphology of the blends and composites was determined through transmission and scanning electron microscopy techniques. Results showed that the compatibilized blends prepared without clay have higher thermal degradation susceptibility and tensile toughness than those prepared with sepiolite and significant changes in complex viscosity and melt elasticity values were observed between them. The nanocomposite blends exhibited similar thermal degradation, lower tensile strength, and Young's modulus values and increased elongation at break and tensile toughness, complex viscosity, and storage modulus compared with those of the nanocomposite of PLA. These results are related to the clay dispersion, to the type of morphology of the different blends, to the localization of the sepiolite in the different phases, the thermomechanical degradation of the PLA matrix phase during melt blending and the grafting degree of the compatibilizers used. POLYM. ENG. SCI., 2012. © 2011 Society of Plastics Engineers     

Efficient sorption of polyphenols to soybean flour enables natural fortification of foods

The present study demonstrated that defatted soybean flour (DSF) can sorb polyphenols from blueberry and cranberry juices while separating them from sugars. Depending on DSF concentration and juice dilution, the concentration of blueberry anthocyanins and total polyphenols sorbed to DSF ranged from 2-22 mg/g and 10-95 mg/g, respectively while the concentration of anthocyanins and proanthocyanidins in cranberry polyphenol-enriched DSF ranged from 2.5-17 mg/g and 21-101 mg/g, respectively. Blueberry polyphenols present in one serving of fresh blueberries (73 g) were delivered in just 1.4 g of blueberry polyphenol-enriched DSF. Similarly, one gram of cranberry polyphenol-enriched DSF delivered the amount of proanthocyanidins available in three 240 ml servings of cranberry juice cocktail. The concentration of blueberry anthocyanins and total polyphenols eluted from DSF remained constant after 22 weeks of incubation at 37 °C, demonstrating the high stability of the polyphenol-DSF matrix. LC-MS analysis of eluates confirmed that DSF retained major cranberry and blueberry polyphenols intact. Blueberry polyphenol-enriched DSF exhibited significant hypoglycaemic activities in C57bl/6J mice, and cranberry polyphenol-enriched DSF showed antimicrobial and anti-UTI activities in vitro, confirming its efficacy. The described sorption process provides a means to create protein-rich food ingredients containing concentrated plant bioactives without excess sugars, fats and water that can be incorporated in a variety of scientifically validated functional foods and dietary supplements.     

Polymer-Drug Conjugates: Novel Carriers for Cancer Chemotherapy

Cancer is the second worldwide cause of death following cardiovascular diseases. Chemotherapy is the gold standard strategy for effective treatment of cancer. However, the use of free chemotherapeutic agents in cancer treatment has been hindered by poor aqueous solubility, short biological half-life, non-speci?city or dose-dependent cellular toxicity, and the development of multidrug resistance. To address the aforementioned limitations, polymer-drug conjugations, among other novel drug delivery approaches, are receiving attention in cancer therapy. In this review the concept of polymer–drug conjugations, polymer–drug conjugates as drug carriers, polymer-drug coupling methods, and recent polymer-anticancer drugs conjugates have been described.     

Emotion enhances the subjective feeling of remembering, despite lower accuracy for contextual details.

Emotion strengthens the subjective experience of recollection. However, these vivid and confidently remembered emotional memories may not necessarily be more accurate. We investigated whether the subjective sense of recollection for negative stimuli is coupled with enhanced memory accuracy for contextual details using the remember/know paradigm. Our results indicate a double-dissociation between the subjective feeling of remembering, and the objective memory accuracy for details of negative and neutral scenes. “Remember” judgments were boosted for negative relative to neutral scenes. In contrast, memory for contextual details and associative binding was worse for negative compared to neutral scenes given a “remember” response. These findings show that the enhanced subjective recollective experience for negative stimuli does not reliably indicate greater objective recollection, at least of the details tested, and thus may be driven by a different mechanism than the subjective recollective experience for neutral stimuli. (PsycINFO Database Record (c) 2011 APA, all rights reserved)