Pulmonary siRNA Delivery with Sophisticated Amphiphilic Poly(Spermine Acrylamides) for the Treatment of Lung Fibrosis.

RNA interference (RNAi) is an efficient strategy to post-transcriptionally silence gene expression. While all siRNA drugs on the market target the liver, the lung offers a variety of currently undruggable targets, which can potentially be treated with RNA therapeutics. To achieve this goal, the synthesis of poly(spermine acrylamides) (P(SpAA) is reported herein. Polymers are prepared via polymerization of N-acryloxysuccinimide (NAS) and afterward this active ester is converted into spermine-based pendant groups. Copolymerizations with decylacrylamide are employed to increase the hydrophobicity of the polymers. After deprotection, polymers show excellent siRNA encapsulation to obtain perfectly sized polyplexes at very low polymer/RNA ratios. In vitro 2D and 3D cell culture, ex vivo and in vivo experiments reveal superior properties of amphiphilic spermine-copolymers with respect to delivery of siRNA to lung cells in comparison to commonly used lipid-based transfection agents. In line with the in vitro results, siRNA delivery to human lung explants confirm more efficient gene silencing of protease-activated receptor 2 (PAR2), a G protein-coupled receptor involved in fibrosis. This study reveals the importance of the balance between efficient polyplex formation, cellular uptake, gene knockdown, and toxicity for efficient siRNA delivery in vitro, in vivo, and in fibrotic human lung tissue ex vivo.

Biomaterials for CO2 Harvesting: From Regulatory Functions to Wet Scrubbing Applications.

A new series of 2-aminoethyl-benzene-based biomaterials, namely, dopamine (DOP), tyramine (TYR), phenylethylamine (PEA), and epinephrine (EPN), dissolved in dimethylsulfoxide (DMSO) have been investigated for CO2 capture upon activatiing their hydhydrochloride salts  with a NaOH pellet. Spectroscopic measurements, including ex situ ATR-FTIR, 1D and 2D NMR experiments have been applied to verify the formation of the sodium carbamate adducts (RR'N-CO2 - Na+). The emergence of new peaks in the IR spectra ranging between 1702 and 1735 cm-1 together with the chemical shift within 157-158 ppm in the 13C NMR, as well as with cross-peaks obtained by 1H-15N HSQC measurements at ca. 84 and 6.6 ppm verified the formation of RR'N-CO2 - Na+ products upon the chemical fixation of CO2. The CO2 sorption capacity of the examined biomaterials was evaluated volumetrically, with a maximum value of 8.18 mmol CO2·g-1 sorbent (36.0 (w/w)%, including both chemisorption and physisorption), for 5 (w/v)% solutions measured at 5 bar CO2 and 25 °C, for TYR and PEA. DFT calculations indicated that the intramolecular hydrogen bonding within the structural motif of EPN-N-CO2 - Na+ adduct provides an exceptional stability compared to monoethanolamine and other structurally related model compounds.

A green sorbent for CO2 capture: α-cyclodextrin-based carbonate in DMSO solution.

Cyclodextrin (α-CD)/KOH pellet dissolved in DMSO was utilized to capture CO2. KOH has a dual function of enhancing the nucleophilicity of the hydroxyl groups on the α-CD rims and acting as a desiccant. 13C NMR spectroscopy provided evidence for the chemisorption of CO2 through the formation of organic carbonate (RO-CO2 -·K+). This was supported by the spectral changes obtained using ex situ ATR-FTIR spectroscopy upon bubbling CO2. Activation of α-CD with NaH or bubbling with 13CO2 verified that chemisorption occurred solely via RO-CO2 -·K+ rather than inorganic bicarbonate. Volumetric gas uptake demonstrated a sorption capacity of 21.3 wt% (4.84 mmol g-1). To the best of our knowledge, this is the highest chemisorption value reported to date for CD-based sorbents. DFT calculations of the Gibbs free energies indicated that the formation of RO-CO2 -·K+ was more favoured at the primary carbinol rather than its secondary counterpart.