Protection of Double-Stranded RNA via Complexation with Double Hydrophilic Block Copolymers: Influence of Neutral Block Length in Biologically Relevant Environments.

Interaction between the anionic phosphodiester backbone of DNA/RNA and polycations can be exploited as a means of delivering genetic material for therapeutic and agrochemical applications. In this work, quaternized poly(2-(dimethylamino)ethyl methacrylate)-block-poly(N,N-dimethylacrylamide) (PQDMAEMA-b-PDMAm) double hydrophilic block copolymers (DHBCs) were synthesized via reversible addition-fragmentation chain-transfer (RAFT) polymerization as nonviral delivery vehicles for double-stranded RNA. The assembly of DHBCs and dsRNA forms distinct polyplexes that were thoroughly characterized to establish a relationship between the length of the uncharged poly(N,N-dimethylacrylamide) (PDMA) block and the polyplex size, complexation efficiency, and colloidal stability. Dynamic light scattering reveals the formation of smaller polyplexes with increasing PDMA lengths, while gel electrophoresis confirms that these polyplexes require higher N/P ratio for full complexation. DHBC polyplexes exhibit enhanced stability in low ionic strength environments in comparison to homopolymer-based polyplexes. In vitro enzymatic degradation assays demonstrate that both homopolymer and DHBC polymers efficiently protect dsRNA from degradation by RNase A enzyme.

Effect of the microstructure of n-butyl acrylate/N-isopropylacrylamide copolymers on their thermo-responsiveness, self-organization and gel properties in water.

HYPOTHESIS: Polymer composition, microstructure, molar mass, architecture… critically affect the properties of thermoresponsive polymers in aqueous media. EXPERIMENTS: The behaviour of n-isopropylacrylamide and n-butyl acrylate-based copolymers of variable composition and structure (statistical, diblock or triblock) was studied in solution at different temperatures and concentrations with turbidimetry measurements, differential scanning calorimetry, electronic microscopy, rheology and scattering experiments. FINDINGS: This study illustrates how it is possible through chemical engineering of the microstructure of amphiphilic thermoresponsive polymers to modulate significantly the self-assembly, morphological and mechanical properties of these materials in aqueous media. Statistical structures induced a strong decrease of cloud point temperature compared to block structures with similar composition. Moreover, block structures lead below the transition temperature to the formation of colloidal structures. Above the transition temperature, the formation of colloidal aggregates is observed at low concentrations, and at higher concentrations the formation of gels. Neutron scattering and light scattering measurements show that for a given composition diblock structures lead to smaller colloids and mesoglobules than their triblock counterparts. Moreover, diblock structures, compared to triblock analogs, allow the formation of gels that do not demix with time (no synaeresis) but that are softer than triblock gels.

Characterisation of polyphosphate coated aluminium-doped titania nanoparticles during milling.

This paper investigates the characterisation of alumina-doped titania nanoparticles, milled under high-shear over time, in the presence of sodium hexametaphosphate (SHMP) dispersant. Transmission electron microscopy (TEM) indicated that prolonged milling times led to the formation of 10 nm particle fines which were electrostatically attracted to larger particles, where no change in the crystal structure was observed. Primary particle sizes measured by dynamic light scattering (DLS) and TEM were in agreement and showed no change in primary particle size (∼250 nm) with respect to milling time, however, there was a clear reduction in the magnitude of the slow mode decay associated to aggregates. The TiO2 was found to have an isoelectric point (iep) in the range of pH 3-4.5, where an increase in milling time led to a lower pHiep, indicative of an increase in SHMP coverage, which was further supported by an intensification in phosphorus content measured by X-ray fluorescence (XRF). Phosphorus content and zeta potential analysis before and after centrifugal washing showed that SHMP was partially removed or hydrolysed for the longer milled pigment samples, whereas no change was observed for shorter milled samples. Relaxation NMR was also performed, where enhanced relaxation rates at longer milling times were associated partially to increases in surface area and exposure of Al sites, as well as physicochemical changes to SHMP density and structure. It is thought that extended milling times may lead to hydrolysis or other structural changes of the dispersant from the high energy milling conditions, allowing easier removal after washing for longer milled pigments.