Myrcene‐Based Tailored Co‐Polymers as Active Pharmaceutical Excipients: Bio‐Based Solutions for Mucoadhesive Excipients

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.