Polyelectrolyte capsules have recently been introduced as new microscopic vehicles which could have high potential in the biomedical field. In this critical review we give an introduction to the layer-by-layer (LbL) technique which is used to fabricate these polyelectrolyte capsules as well as to the different triggers that have been exploited to obtain drug release from these capsules. Furthermore, other types of triggered delivery systems are compared and critically discussed with regard to their clinical relevance. (171 references.).

West Nile virus (WNV) is continuously spreading across Europe, and other continents, i.e. North and South America and many other regions of the world. Despite the overall sporadic nature of outbreaks with cases of West Nile neuroinvasive disease (WNND) in Europe, the spillover events have increased and the virus has been introduced into new areas. The high genetic diversity of the virus, with remarkable phenotypic variation, and its endemic circulation in several countries, require an intensification of the integrated and multidisciplinary research efforts built under the 7th Framework Programme of the European Union (FP7). It is important to better clarify several aspects of WNV circulation in Europe, including its ecology, genomic diversity, pathogenicity, transmissibility, diagnosis and control options, under different environmental and socio-economic scenarios. Identifying WNV endemic as well as infection-free areas is becoming a need for the development of human vaccines and therapeutics and the application of blood and organs safety regulations. This review, produced as a joint initiative among European experts and based on analysis of 118 scientific papers published between 2004 and 2014, provides the state of knowledge on WNV and highlights the existing knowledge and research gaps that need to be addressed with high priority in Europe and neighbouring countries

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Ellagic acid (EA) is a naturally occurring plant polyphenol formed by the hydrolysis of ellagitannins, which are primarily found in grapes, nuts and fruits. EA has been known to have potent anticarcinogenic activities, however, its insolubility under physiological conditions limits its potential applications. In this work, we have prepared complexes of ellagic acid with peptide nanotubes and polycations such as low molecular weight polyethylenimine (PEI), polyarginine and polylysine to enhance its properties for drug delivery. In particular, polycations such as PEI are well known non-viral vectors. Briefly, EA nanofibers were grown by self-assembly and were complexed with peptide nanotubes or poly cations at varying temperature and pH. The formation of the nanocomplexes was confirmed by zeta-potential analysis. The morphologies of the complexes were examined by electron microscopy. Because of the rigid core of EA that offers shape consistence, and the poly-cation shells that passivate the surfaces, coreÀshell nanoconjugates whose average diameters were dependent upon the concentrations and pH were formed. In the formed complexes, the charged amine groups of the polycations most likely interact with the partially deprotonated carboxylate and hydroxyl groups of EA. In some cases, the EA was coupled with rhodamine to examine the effect of bound versus unbound nanocomplexes formed using confocal microscopy. The interactions of the complexes with mammalian cells were examined by live-cell imaging in the presence of normal rat kidney cells. The anticarcinogenic effects of the nanoprobes was explored using HeLa cells. Finally, the ability of the nanocomplexes for drug release was examined at varying pH and concentrations. Such nanocomplexes may have potential applications not only for anticarcinogenic activities but may also help probe mechanisms involved with EA based biodegradable polycationic-based delivery and cellular attachment towards use in varying therapeutic applications.

Cystic fibrosis (CF) is characterized by the presence of a viscoelastic mucus layer in the upper airways and bronchi. The underlying problem is a mutation in the gene encoding the cystic fibrosis transmembrane conductance regulator protein. Clinical studies of gene transfer for CF are ongoing. For gene delivery to the airways of CF patients to be effective, the mucus covering the target cells must be overcome. We therefore examined the extent to which CF sputum presents a physical barrier to the transport of nanospheres of a size comparable to that of lipoplexes and other transfection systems currently being clinically evaluated for CF gene therapy. We observed that an extremely low percentage of nanospheres (< 0.3%) moved through a 220-microm-thick CF sputum layer after 150 min. The largest nanospheres studied (560 nm) were almost completely blocked by the sputum, whereas the smaller nanospheres (124 nm) were retarded only by a factor of 1.3 as compared with buffer. Surprisingly, the nanospheres diffused significantly more easily through the more viscoelastic sputum samples. We hypothesize that the structure of the network in sputum becomes more macroporous when the sputum becomes more viscoelastic. Sputum from a patient with chronic obstructive pulmonary disease retarded the transport of nanospheres to the same extent as did CF sputum. When directly mixed with CF sputum, recombinant human deoxyribonuclease I moderately facilitated the transport of nanospheres through CF sputum.

Gene complexes with optimal physicochemical characteristics for cystic fibrosis (CF) gene therapy in vitro may become inactive in vivo as a result of destruction upon interaction with CF mucus. Therefore, we examined in this study to what extent main sputum components (linear DNA, mucin, phosphatidylcholine, phosphatidylglycerol, and albumin) may disintegrate lipoplexes. We found that mixing linear DNA with lipoplexes, in concentration ratios as occurs in the mucus of patients with CF in clinical studies with lipoplexes, drastically altered the surface charge and size of our lipoplexes and resulted in the liberation of plasmid DNA from the lipoplexes. These concentration ratios occur in vivo when the DNA concentration in the sputum becomes > 2.7 mg/ml, a quite realistic concentration even in patients without acute exacerbations. Lipoplexes brought in contact with native CF sputa at clinically relevant concentration ratios dissociated when the DNA concentration in the sputa was > 2.7 mg/ml. However, when the linear DNA was degraded by recombinant human deoxyribonuclease I before lipoplexes were added, the linear DNA did not cause any dissociation of the lipoplexes. Addition of albumin and mucin to the lipoplexes in a clinically relevant concentration ratio changed the surface charge of the lipoplexes to negative, however, without release of plasmid DNA. Mucin, dipalmitoylglycerophosphocholine, and dipalmitoylglycerophosphoglycerol did not cause any change in lipoplex properties at clinically relevant concentration ratios.

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