Pharmakologisch aktive polymere, 8.Poly[2‐(methylsulfinyl)äthylacrylat]e und ihre vermittelnde wirkung auf die transkutane resorption von pharmaka

Abstract

ZUSAMMENFASSUNG:Poly [2-(methylsulfinyl)athylacrylat] (2a) und Poly[2-(methylsulfinyl)athylmethacrylat] (2b) wurden synthetisiert und auf ihre vermittelnde Wirkung bei transkutaner Resorption einiger Pharmaka untersucht. 2b verbesserte die Resorption der Phosphorsaureester Dimethoat@ und Paraoxon@ und der p-Aminohippursaure und war etwa mit der Wirksamkeit von DMSO vergleichbar.Ein geringer penetrationsfordernder Effekt ergab sich fur Dinitrochlorbenzol. Nicht beeinflurjt wurde die dermale Resorption von Isoprenalinsulfat. Die beiden Polymeren zeigten eine gute Lokalvertraglichkeit und 2b auch keine akute Allgemeintoxizitat bei systematischer Anwendung. Der fur DMSO charakteristische knoblauchartige Geruch trat nach lokaler und systemischer Anwendung der beiden Polymeren nicht auf. SUMMARY:Poly[2-(methylsulfinyl)ethyl acrylate] (2a) and poly[2-(methylsulfinyl)ethyl methacrylate] (2b) were synthesized in order to examine their ability to enhance the penetration of pharmaceutical agents through the skin. 2b improved the absorption of the two phosphoric acid esters Dimethoat@ and Paraoxon' as well as that of p-aminohippuric acid by an amount which was comparable to the effect shown by DMSO.A smaller effect was observed in thecase ofdinitrochlorobenzene. The dermal absorption of isoprenalin sulfate was not influenced. Both polymers showed a good local compatibility and 2b no acute common toxicity at systemic levels of application. The characteristic garlic-like odor of DMSO was not observed after either local or systemic application of the polymers. '1 7. Mitteilung cf. ''.

Main Chain Polysulfoxides as Active ‘Stealth’ Polymers with Additional Antioxidant and Anti-Inflammatory Behaviour

“…Polymers based on sulfoxides are known for their very low cytotoxicity [29,30,31], and the idea to use them in a biological environment is not new. In the mid 1970s, Helmut Ringsdorf already saw the potential advantages of sulfoxide-containing polymers and studied side-chain sulfoxide polyacrylates (in particular poly(2-(methylsulfinyl)ethyl acrylate), PMSEA) as biocompatible and bioresorbable penetration enhancers [32]. PMSEA was recently proposed again by Matyjaszewski with more modern syntheses based on Atom Transfer Radical Polymerization (ATRP) [29], electrochemically mediated ATRP (eATRP) [33], and surface-initiated ATRP [34].…”

Oxidation-Responsive and “Clickable” Poly(ethylene glycol) via Copolymerization of 2-(Methylthio)ethyl Glycidyl Ether

“…However, in contrast to regular ethers, the nature of sulfur provides the possibility to functionalize thioethers via oxidation, alkylation, and alkoxylation, − which can lead to interesting material properties. In the 1970s, Ringsdorf and co-workers demonstrated that oxidized poly­[2-(methylsulfinyl)­ethyl acrylate] and poly­[2-(methylsulfinyl) methacrylate] can serve as polymeric resorption enhancing alternatives to low molecular weight DMSO. , Thirty years later, Hubbell, Tirelli, and co-workers recognized the potential of polythioethers as redox-responsive nanocarriers for inflammation targeting . In the oxidative milieu of inflamed tissue, hydrophobic thioethers are oxidized to more polar sulfoxides or sulfones, leading to a change in the hydrophobic/hydrophilic balance with disassembly of the nanostructure.…”

Oxidant‐Dependent REDOX Responsiveness of Polysulfides

“…The knowledge of the oxidized products is also important: sulfoxide‐containing polymers were initially studied by the group of Ringsdorf in the 1970s with very promising results in terms of extremely low in vivo toxicity 41, 42. On the other hand, low‐molecular‐weight depolymerization products and/or sulfone‐containing substrates may be considerably more toxic.…”