Successful therapeutic delivery of siRNA with polymeric nanoparticles seems to be a promising but not vastly understood and complicated goal to achieve. Despite years of research, no polymer-based delivery system has been approved for clinical use. Polymers, as a delivery system, exhibit considerable complexity and variability, making their consistent production a challenging endeavor. However, a better understanding of the polymerization process of polymer excipients may improve the reproducibility and material quality for more efficient use in drug products. Here, we present a combination of Design of Experiment and Python-scripted data science to establish a prediction model, from which important parameters can be extracted that influence the synthesis results of polybeta-amino esters (PBAEs), a common type of polymer used preclinically for nucleic acid delivery. We synthesized a library of 27 polymers, each one at different temperatures with different reaction times and educt ratios using an orthogonal central composite (CCO-) design. This design allowed a detailed characterization of factor importance and interactions using a very limited number of experiments. We characterized the polymers by analyzing the resulting composition by 1H-NMR and the size distribution by GPC measurements. To further understand the complex mechanism of block polymerization in a one-pot synthesis, we developed a Python script that helps us to understand possible step-growth steps. We successfully developed and validated a predictive response surface and gathered a deeper understanding of the synthesis of polyspermine-based amphiphilic PBAEs.

Thermo-responsive diblock copolymer, poly(N-isopropylacrylamide)-block-poly(N-vinylisobutyramide) was synthesized via switchable reversible addition-fragmentation chain transfer (RAFT) polymerization and its thermal transition behavior was studied. Poly(N-vinylisobutyramide) (PNVIBA), a structural isomer of poly(N-isopropylacrylamide) (PNIPAM) shows a thermo-response character but with a higher lower critical solution temperature (LCST) than PNIPAM. The chain extension of the PNVIBA block from the PNIPAM block proceeded in a controlled manner with a switchable chain transfer reagent, methyl 2-[methyl(4-pyridinyl)carbamothioylthio]propionate. In an aqueous solution, the diblock copolymer shows a thermo-responsive behavior but with a single LCST close to the LCST of PNVIBA, indicating that the interaction between the PNIPAM segment and the PNVIBA segment leads to cooperative aggregation during the self-assembly induced phase separation of the diblock copolymer in solution. Above the LCST of the PNIPAM block, the polymer chains begin to collapse, forming small aggregates, but further aggregation stumbled due to the PNVIBA segment of the diblock copolymer. However, as the temperature approached the LCST of the PNVIBA block, larger aggregates composed of clusters of small aggregates formed, resulting in an opaque solution.

Our society has been pursuing high-performance biodegradable polymers made from facile methods and readily available monomers. Here, we demonstrate a library of enzyme-degradable polymers with desirable properties from the first reported step polyaddition of diamines, COS, and diacrylates. The polymers contain in-chain ester and thiourethane groups, which can serve as lipase-degradation and hydrogen-bonding physical crosslinking points, respectively, resulting in possible biodegradability as well as upgraded mechanical and thermal properties. Also, the properties of the polymers are scalable due to the versatile method and the wide variety of monomers. We obtain 46 polymers with tunable performance covering high-Tm crystalline plastics, thermoplastic elastomers, and amorphous plastics by regulating polymer structure. Additionally, the polymerization method is highly efficient, atom-economical, quantitatively yield, metal- and even catalyst-free. Overall, the polymers are promising green materials given their degradability, simple and modular synthesis, remarkable and tunable properties, and readily available monomers.

Plant cell wall researchers were asked their view on what the major unanswered questions are in their field. This article summarises the feedback that was received from them in five questions. In this issue you can find equivalent syntheses for researchers working on bacterial, unicellular parasite and fungal systems.

Researchers have been chasing plastics that can automatically and fully degrade into valuable products under natural conditions. Here, we develop a series of water-degradable polymers from the first reported fast and selective cationic copolymerization of formaldehyde (B) with cyclic anhydrides (A). In addition to readily accessible monomers, the method is performed at industrially relevant temperatures (~100 °C), takes tens or even minutes, and uses common acid as the catalyst. Interestingly, such polymers possess tunable AB/ABB-type repeating units, which are considered to be thermodynamic and kinetic products, respectively, resulting in low carbon content ([O] : [C] up to 1 : 1). Notably, the polymers can completely degrade to valuable diacids within 150 days in water at ambient temperature owing to the incorporation of carboxyl terminals and acid-responsive acetal units. By washing with aqueous sodium carbonate, the polymers are relatively stable over several months.

In the field of non-oxide ceramics, the polymer-derived ceramic (PDC) approach appears to be very promising, especially for obtaining easily shaped and homogeneous materials in terms of structure and composition. However, in order to reach a suitable form during the process, it is often necessary to study the rheology of preceramic polymers while they are modified during polymerisation or crosslinking reactions. Given this need in the understanding of the real-time rheology of macromolecules during their synthesis, a rheometer coupled with both an infrared spectrometer and a Raman probe is described as a powerful tool for monitoring in situ synthesised polycarbosilanes. Indeed, this original device allows one to control the viscosity of a hyberbranched polycarbosilane from defined difunctional and tetrafunctional monomers. Meanwhile, it links this evolution to structural modifications in the macromolecular structure (molar masses, dispersity and conformation), based on SEC-MALS analyses, synchronised by the monomer conversion determined by using Raman and infrared spectroscopies, a common denominator of the aforementioned instrumental platform.

The facile synthesis of chemically recyclable polymers derived from sustainable feedstocks presents enormous challenges. Here, we develop a novel, modular, and efficient click reaction for connecting primary, secondary, or tertiary alcohols with activated alkenes via a bridge molecule of carbonyl sulfide (COS). The click reaction is successfully applied to synthesize a series of recyclable polymers by the step polyaddition of diols, diacrylates, and COS. Diols and diacrylates are common chemicals and can be produced from biorenewable sources, and COS is released as the industrial waste. In addition to sustainable monomers, the approach is atom-economical, wide in scope, metal-free, and performed under mild conditions, affording unprecedented polymers with nearly quantitative yields. The produced polymers also possess predesigned and widely tunable structure owing to the versatility of our method and the broad variety of monomers. The in-chain thiocarbonate and ester polar groups can play as breakpoints, allowing these polymers to be easily recycled. Overall, the polymers have broad prospects for green materials given their facile synthesis, readily available feedstocks, desirable performance, and chemical recyclability.

Various polymeric nanoparticles have been used as drug carriers in drug delivery systems (DDSs). Most of them were constructed from dynamic self-assembly systems formed via hydrophobic interactions and from structures that are unstable in an in vivo environment owing to their relatively weak formation forces. As a solution to this issue, physically stabilized core-crosslinked particles (CP) with chemically crosslinked cores have received attention as alternatives to the dynamic nanoparticles. This focused review summarizes recent advances in the construction, structural characterization, and in vivo behavior of polymeric CPs. First, we introduce a nanoemulsion-mediated method to create polyethylene glycol (PEG)-bearing CPs and their structural characterization. The relationship between the PEG chain conformations in the particle shell and the in vivo fate of the CPs is also discussed. After that, the development and advantages of zwitterionic amino acid-based polymer (ZAP)-bearing CPs are presented to address the poor penetration and the internalization of PEG-based CPs into tumor tissues and cells, respectively. Finally, we conclude and discuss prospects for application of polymeric CPs in the DDS field.

Integrating nucleic acid extraction in amplification-based point-of-care diagnostics will be a significant feature for next-generation point-of-care virus detection devices. However, extracting DNA efficiently on a microfluidic chip poses many technological and commercialization challenges, including manual steps, multiple instruments, pretreatment processes, and the use of organic solvents (ethanol, IPA) that inhibit detection, which is not viable with routine testing such as viral load monitoring of transplant patients for post-operative care. This paper presents a microfluidic system capable of two-step DNA extraction from blood using a UV-assisted hyperbranched poly(β-amino ester) (HPAE)-modified silica membrane for cytomegalovirus (CMV) detection in a rapid and instrument-free manner without the presence of amplification inhibitors. HPAEs of varying branch ratios were synthesized, screened, and coated on a silica membrane and bonded between two layers of poly(methyl methacrylate) (PMMA) substrates. Our system could selectively extract DNA from blood with an efficiency of 94% and a lower limit viral load of 300 IU/mL in 20 min. The extracted DNA was used as the template for real-time loop-mediated isothermal amplification (LAMP)-based detection of CMV and was found to produce a fluorescent signal intensity that was comparable with commercially extracted templates. This system can be integrated easily with a nucleic acid amplification system and used for routine rapid testing of viral load in patient blood samples.

A rich plethora of information about grafted chitosan (CS) for medical use has been reported. The capability of CS-grafted poly(N-hydroxyethyl acrylamide) (CS-g-PHEAA) to support human dermal fibroblasts (HDFs) in vitro has been proven. However, CS-grafted copolymers lack good stiffness and the characteristic microstructure of a cellular matrix. In addition, whether CS-g-PHEAA can be used to prepare a scaffold with a suitable morphology and mechanical properties for skin tissue engineering (STE) is unclear. This study aimed to show for the first time that step-growth polymerizations can be used to obtain polyurethane (PU) platforms of CS-g-PHEAA, which can also have enhanced microhardness and be suitable for in vitro cell culture. The PU prepolymers were prepared from grafted CS, polyethylene glycol, and 1,6-hexamethylene diisocyanate. The results proved that a poly(saccharide-urethane) [(CS-g-PHEAA)-PU] could be successfully synthesized with a more suitable microarchitecture, thermal properties, and topology than CS-PU for the dynamic culturing of fibroblasts. Cytotoxicity, proliferation, histological and immunophenotype assessments revealed significantly higher biocompatibility and cell proliferation of the derivative concerning the controls. Cells cultured on (CS-g-PHEAA)-PU displayed a quiescent state compared to those cultured on CS-PU, which showed an activated phenotype. These findings may be critical factors in future studies establishing wound dressing models.