Anionic liposomes for small interfering ribonucleic acid (siRNA) delivery to primary neuronal cells: Evaluation of alpha-synuclein knockdown efficacy

Alpha-synuclein (α-syn) deposition in Lewy bodies (LB) is one of the main neuropathological hallmarks of Parkinson's disease (PD).LB accumulation is considered a causative factor of PD,which suggests that strategies aimed at reducing α-syn levels could be relevant for its treatment.In the present study,we developed novel nanocarriers suitable for systemic delivery of small interfering ribonucleic acid (siRNA) that were specifically designed to reduce neuronal α-syn by RNA interference.Anionic liposomes loaded with an siRNA-protamine complex for α-syn gene silencing and decorated with a rabies virus glycoprotein (RVG)-derived peptide as a targeting agent were prepared.The nanoparticles were characterized for their ability to load,protect,and deliver the functional siRNA to mouse primary hippocampal and cortical neurons as well as their efficiency to induce gene silencing in these cells.Moreover,the nanocarriers were evaluated for their stability in serum.The RVG-decorated liposomes displayed suitable characteristics for future in vivo applications and successfully induced α-syn gene silencing in primary neurons without altering cell viability.Collectively,our results indicate that RVG-decorated liposomes may be an ideal tool for further studies aimed at achieving efficient in vivo α-syn gene silencing in mouse models of PD.     

Erratum to: Anionic liposomes for small interfering ribonucleic acid (siRNA) delivery to primary neuronal cells: Evaluation of alpha-synuclein knockdown efficacy

Nano Research - The name of the fourth author in the original version of this article was unfortunately wrongly written on the first page. Instead of Caitriona M. O’iscoll It should read...     

Chemical and biological modification of cynaropicrin and grosheimin: a structure–bitterness relationship study

This work is part of a plan to investigate the structure–bitterness relationship in sesquiterpene lactones of dietary origin. The major guaianolides from artichoke (Cynara scolimus L) were chosen for this study because of their exceedingly bitter taste and well‐proven safety at concentrations currently employed in alcoholic beverages. Moreover they are available from horticultural left‐overs and amenable to a wide range of chemical modifications. We isolated cynaropicrin and grosheimin from artichoke leaves and used either chemical modification or bioconversion by basidiomycetes to prepare a number of derivatives which were submitted to a panel test for sensory evaluation. Bitterness variations appeared to be related to changes in molecule polarity. Bitter taste was markedly abated by either the loss of exomethylenes or the opening of the lactone ring. Copyright © 2005 Society of Chemical Industry     

Synthesis of cyclodextrin‐based polymers and their use as debittering agents

Cyclodextrins (CDs) and their derivatives are used to suppress unpleasant tastes and odors or to achieve a controlled release of certain food constituents. This article describes the synthesis by nonconventional methods of (1) crosslinked, insoluble CD polymers and (2) water‐soluble, CD‐grafted carboxymethylchitosan and carboxymethylcellulose. The CD polymers were obtained by the reaction of β‐CD with one of the following crosslinking agents: epichlorohydrin, diphenyl carbonate, or hexamethylene diisocyanate. Their preparations were usually carried out under high‐intensity ultrasound, which resulted in much shorter reaction times and narrower distributions of particle size (as determined by scanning electron microscopy measurements). A novel, insoluble CD polymer was obtained by reticulation under microwaves of propargyl‐β‐CD with 1,3‐bis(azidomethyl)benzene through Huisgen 1,3‐dipolar cycloaddition. Short columns packed with the insoluble polymers were found to efficiently sequester naringin from aqueous solutions; successively, they could be easily regenerated by a counter‐current ethanol wash that also achieved an excellent recovery of the flavonoid. Differential scanning calorimetry thermograms showed that the crosslinked CD polymers formed inclusion complexes with naringin. The soluble polymers also interacted with bitter flavonoids of citrus fruits (naringin and limonin), as shown by the results of sensorial panel tests, in which they behaved as bitter‐masking agents. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Relationships between microstructure and transport properties of proton-conducting porous PVDF membranes

Fluorinated polymers are today investigated as possible alternatives to Nafion™ in PEM Fuel Cells. In this paper, we study the relationships between the microstructure and the proton transport of porous PVDF homopolymer membranes swollen by 11 M aqueous solution of H₃PO₄. The analysis is performed on membranes with different nominal pores size values, d_p. The membranes are thermally stable at least up to 250 °C. A dependence of the proton transport on the pores size has been found, that is particularly evident for low d_p values and at low relative humidity (R.H.). Conductivity values exceeding 0.1 S cm⁻¹ are obtained at 80 °C even at 10% R.H. for d_p ≥ 0.22 μm. We show that the behaviour of the transport properties cannot be simply rationalized in terms of d_p, but it requires an accurate knowledge of the membrane microstructure (tortuosity, pores interconnections and size distributions). ³¹P NMR spectroscopy also shows that anisotropic interactions take place between the components of the solution and at a lower extent, between the solution and the pores walls, also for d_p values in the micrometer range. In order to make a preliminary check of the suitability of these membranes for applications in Direct Methanol Fuel Cells (DMFCs), studies of methanol crossover and diffusion through the membrane have been carried out and compared with those of Nafion™.     

Biotransformation of (−)‐bornyl acetate using submerged cultures of Collybia velutipes,Trametes hirsuta and Ganoderma applanatum

The biotransformation of (?)‐bornyl acetate by three Basidiomycetes, Collybia velutipes, Trametes hirsuta and Ganoderma applanatum was monitored for 7 days. The observed reactions were regio‐ and stereo‐selective hydroxylation, acetate hydrolysis and oxidation of alcohols to carbonyl compounds. Nine cyclic compounds, three of which (6‐exo‐hydroxybornyl acetate, 8‐hydroxy‐5‐exo‐hydroxybornyl acetate, 9‐hydroxy‐5‐exo‐hydroxybornyl acetate), not previously described, were isolated from the fermentation broth and therefore were identified. Product types and concentrations varied with strain and incubation time. The toxicity of the substrate was assessed from the variation of fungal biomass in the course of incubation. Copyright © 2005 Society of Chemical Industry     

Bicompartmental device for dynamic cell coculture: design, realisation and preliminary results

Low-shear perfusion and compartmental systems are very important conceptual designs for the realization of high-density cell cultures and cocultures, thus allowing very realistic models and therefore reliable results. In this work, we combines low-shear perfusion and multi-compartments in one device. We also describe the design, fabrication and validation of a bicompartmental, low-perfusion culture chamber specifically designed for applications in various fields, such as tissue engineering, pharmacology, molecular biology, pharmacokinetics, nanomedicine, and drug delivery testing. The device properties in terms of flow features and metabolite exchange capabilities are fully characterized. In vitro tests performed on cell lines confirm the effectiveness of the device as an experimental tool for measurements in dynamic and multiple-cell cultures and cocultures.     

Analysis and development of locomotion devices for the gastrointestinal tract

The authors are developing devices for semi-autonomous or autonomous locomotion in the gastrointestinal (GI) tract. In this paper, they illustrate the systematic approach to the problem of "effective" locomotion in the GI tract and the critical analysis of "inchworm" locomotion devices, based on extensor and clamper mechanisms. The fundamentals of locomotion and the practical problems encountered during the development and the testing (in vitro and in vivo) of these devices are discussed. A mini device capable of propelling itself in the colon and suitable to perform, at least, rectum-sigmoidoscopy (the tract where approximately 60% of all colon cancers are found) is presented. This paper introduces preliminary, but useful, concepts for understanding, modeling and improving the performance of virtually any existing and novel devices for endoscopy of the GI tract.