Vahid Ahmadi

Background/Objectives: A push–pull osmotic pump (PPOP) tablet is a controlled-release delivery system consisting of a bilayer tablet (push layer/pull (drug) layer), coated within a selectively permeable barrier membrane, and containing a laser-drilled orifice in the pull layer side of the barrier. Aqueous media permeates across the barrier membrane and into the bilayer tablet core. The push layer swells axially, creating force and acting like a piston to drive the active pharmaceutical ingredient (API) dosage through the laser-drilled orifice. The primary purpose of this study was to develop a method to quantitate swelling force generated by the PPOP push layer. Methods: A key challenge was devising measurement methodology that most closely represented continuous PPOP push-layer swelling force exerted in the axial dimension over time, so the method setup was adjusted until attaining what closely approximated PPOP push-layer swelling-force dynamics within the delivery system. After some adjustments, swelling forces were measured from PPOP push layers containing various polyethylene oxide (PEO) molecular weight (MW) grades. Results: The most representative configuration was a cylindrical holder fully submerged in water with the push-layer compact situated at the bottom of the holder. This setup constrained the push layer to swell in the axial dimension. The optimal setup also allowed the texture analyzer to continuously measure push-layer swelling force over 24 h, representing typical duration of functionality. Quantitative analysis of the swelling force vs. time profiles demonstrated comparable force generation over 24 h from the 4, 5, and 7,000,000 MW grades of PEO. Swelling force decreased in near-linear fashion, from push layers formulated with PEO 4,000,000 down to PEO 100,000. Conclusions: The optimal setup enabled discriminatory quantification of push-layer swelling force for PEO MW grades spanning from 100,000 up to 4,000,000 Daltons. Furthermore, the method demonstrated why the 4, 5, and 7,000,000 MW grades of PEO are recommended for use in the PPOP push layer, given that these three highest MW grades delivered comparable swelling force over 24 h. Finally, the method provides new quantitative insight into the push-layer swelling force that is necessary, over the duration of the dosing interval, to deliver the active dosage from the PPOP tablet.

Mucine sind eine Schlüsselkomponente der defensiven Schleimbarriere. Es handelt sich um ausgedehnte Fasern mit sehr hohem Molekulargewicht, deren vielfältige biologische Funktionen stark von ihren spezifischen Strukturparametern abhängen. Hier stellen wir eine Mucin‐inspirierte Nanostruktur basierend auf dendronisierten Polysulfaten auf Methacrylatbasis (MIP‐1) mit hohem Molekulargewicht (MW=450 kDa) vor. Das Thiol‐End‐funktionalisierte Mucin‐inspiriertem Polymer (MIP) wurde durch RAFT‐Polymerisation im Multi‐Gramm‐Maßstab hergestellt. Die Kryo‐Elektronentomographie‐Analyse (Kryo‐ET) von MIP‐1 bestätigte eine Mucin‐artige, wurmartige einkettige Faserstruktur (Länge=144±59 nm) in wässriger Lösung. Diese biokompatible Faser zeigte eine vielversprechende Aktivität mit einer bemerkenswert niedrigen mittleren inhibitorischen Konzentration (IC₅₀, mit IC₅₀=10.0 nM) gegenüber SARS‐CoV‐2 und dessen Mutantenstamm. Darüber hinaus untersuchen wir die Auswirkungen der Faserlänge auf die Hemmung gegenüber SARS‐CoV‐2, indem wir andere funktionelle Polymere (MIPs) mit unterschiedlichen Faserlängen miteinander vergleichen.

Mucins are the key component of the defensive mucus barrier. They are extended fibers of very high molecular weight with diverse biological functions depending strongly on their specific structural parameters. Here, we present a mucin‐inspired nanostructure, produced via a synthetic methodology to prepare methacrylate‐based dendronized polysulfates (MIP‐1) on a multi gram‐scale with high molecular weight (MW=450 kDa) and thiol end‐functionalized mucin‐inspired polymer (MIP) via RAFT polymerization. Cryo‐electron tomography (Cryo‐ET) analysis of MIP‐1 confirmed a mucin‐mimetic wormlike single‐chain fiber structure (length=144±59 nm) in aqueous solution. This biocompatible fiber showed promising activity against SARS‐CoV‐2 and its mutant strain, with a remarkable low half maximal (IC₅₀) inhibitory concentration (IC₅₀=10.0 nM). Additionally, we investigate the impact of fiber length on SARS‐CoV‐2 inhibition by testing other functional polymers (MIPs) of varying fiber lengths.

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.

A broad-spectrum heteromultivalent influenza inhibitor is developed by using the host cell membrane on an inverted virus scaffold.