Two thermoresponsive polyacrylamides based on the 2,6-diaminopyridine motif were synthesized and their UCST-type reversible thermoresponsive behaviour was studied in water/alcohol mixtures.

Poor water solubility and low bioavailability of active pharmaceutical ingredients (APIs) are major causes of friction in the pharmaceutical industry and represent a formidable hurdle for pharmaceutical drug development. Drug delivery remains the major challenge for the application of new small-molecule drugs as well as biopharmaceuticals. The three challenges for synthetic delivery systems are: (i) controlling drug distribution and clearance in the blood; (ii) solubilizing poorly water-soluble agents, and (iii) selectively targeting specific tissues. Although several polymerbased systems have addressed the first two demands and have been translated into clinical practice, no targeted synthetic drug delivery system has reached the market. This Review is designed to provide a background on the challenges and requirements for the design and translation of new polymer-based delivery systems. This report will focus on chemical approaches to drug delivery for systemic applications.

Here, we report the topology-matched design of heteromultivalent nanostructures as potent and broad-spectrum virus entry inhibitors based on the host cell membrane. Initially, we investigate the virus binding dynamics to validate the better binding performance of the heteromultivalent moieties as compared to homomultivalent ones. The heteromultivalent binding moieties are transferred to nanostructures with a bowl-like shape matching the viral spherical surface. Unlike the conventional homomultivalent inhibitors, the heteromultivalent ones exhibit a half maximal inhibitory concentration of 32.4 ± 13.7 μg/ml due to the synergistic multivalent effects and the topology-matched shape. At a dose without causing cellular toxicity, >99.99% reduction of virus propagation has been achieved. Since multiple binding sites have also been identified on the S protein of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), we envision that the use of heteromultivalent nanostructures may also be applied to develop a potent inhibitor to prevent coronavirus infection.

A straightforward and gram-scale synthesis method was developed to engineer virucidal heparin-mimicking polymers as HSV-1 inhibitors.

Polymerization processes with high reproducibility, traceability, and nontoxic compounds are required for biomedical applications. Here an automated solvent‐free polymerization of hyperbranched polyglycerol has been established on a multiple‐hundred gram scale. Performed is an anionic ring‐opening multibranching (ROMB) polymerization with slow addition of glycidol. The solvent‐free approach avoids commonly used organic solvents during the polymerization and work‐up. Due to the automation of the polymerization process a high reproducibility and traceability is accomplished. The used reactor is equipped with an anchor stirrer and stirrer control, which measures the applied torque. A linear correlation of the increasing torque and the degree of polymerization is observed, which can be used to monitor the molecular weight in situ during the polymerization.