Annabelle Knoll

Mucoadhesive polymers are widely used in drug delivery to prolong residence time on mucus‐covered surfaces and enhance drug bioavailability, but conventional systems often suffer from broad molecular weight distributions and inconsistent performance. Here, three different amphiphilic co‐polymers based on bio‐sourced myrcene and PEG‐methacrylate are synthesized via Reversible Addition–Fragmentation Chain Transfer polymerization, yielding well‐defined polymers with narrow molar mass distributions. Structural analyses using ¹ H NMR spectroscopy and gel permeation chromatography confirm predominant 1,4‐addition and low dispersity. Energy‐filtered transmission electron microscopy and dynamic light scattering show self‐assembled nanostructures with mean diameters below 60 nm. In vivo toxicity evaluation in Galleria mellonella larvae demonstrates 100% survival after 48 h and prolonged polymer residence compared with PEG_4000. Mucoadhesion and mucopermeation assays reveal enhanced adhesion with intestinal mucus, with up to 50% retention after 3 h, a 6.6‐fold increase in mucus viscosity, and limited permeation (∼20%) into the mucus gel. Additionally, the polymers exhibit pronounced antioxidant activity (EC ₅₀ = 0.05% (m/V)) and antimicrobial activity against Escherichia coli ( E. coli ). Overall, high regioselectivity and controllable polymerization, combined with strong interactions with the intestinal mucosa, low toxicity, and biological effects, indicate that myrcene‐based co‐polymers are promising bio‐sourced candidates for use as active excipients in drug delivery.

Two β-cyclodextrin conjugates differing in their sulfur-bearing substituent, 1,2-dithiolane versus free thiols, were synthesized and evaluated as crosslinkers for polymeric mucin glycoproteins and thiolated polysaccharides, providing a comparison of ring-strain-driven thiol-disulfide exchange and oxidative disulfide formation. Per-thiolated β-cyclodextrin (β-CD-SH) was prepared via complete substitution of hydroxyl groups using phosphorous pentasulfide, while α-lipoic acid modified β-cyclodextrin (β-CD-LA) was obtained via esterification, introducing strained 1,2-dithiolane moieties as exchange-reactive disulfide units. Structural characterization by ¹H NMR and colorimetric assays confirmed successful functionalization of both derivatives. Safety profiles of the modified β‑cyclodextrins were evaluated regarding cytotoxicity, hemolysis, free radical interactions, and biodegradation. Rheological studies revealed stronger crosslinking (5.7-fold) of β-CD-LA with mucus glycoproteins compared to β-CD-SH, resulting in substantial viscosity enhancement and reduced diffusion through model mucus layers. Furthermore, β-CD-LA increased the viscosity of thiolated alginate by 22.1-fold and of thiolated xanthan by 77.3-fold, indicating rapid formation of disulfide-mediated polymer networks. These findings place the two β-cyclodextrin conjugates into distinct mechanistic categories: strain-activated dithiolane versus oxidation-driven thiol systems. This demonstrates that 1,2-dithiolane functionalization represents a superior strategy over free thiols for introducing dynamic covalent crosslinking capability into cyclodextrin-based scaffolds, supporting the use of dithiolane-bearing cyclodextrins as versatile multiarm crosslinkers for polymer network formation.