Mucoadhesive amphiphilic polymers for buccal drug delivery: overcoming solubility and permeation barriers

Buccal drug delivery offers a non-invasive and patient-friendly alternative to conventional oral administration because of its rapid onset of action and capacity to avoid hepatic first-pass metabolism. However, drugs' poor water solubility, quick salivary clearance, enzymatic degradation, and brief mucosal residence times frequently limit their therapeutic efficacy and bioavailability. In recent years, mucoadhesive-amphiphilic polymers have emerged as a potential remedy for these associated issues. Mucoadhesive polymers extend their stay at the buccal mucosa through hydrogen bonding, electrostatic interactions, and chain interpenetration with mucin glycoproteins, whereas amphiphilic modification adds hydrophobic domains that can solubilize and preserve weakly water-soluble medications. The mechanisms underlying mucoadhesion, how to impart amphiphilicity to natural biopolymers such as chitosan, pectin, alginate, pullulan, carrageenan, and gum, and how these biopolymers self-assemble into useful nanostructures such as hydrogels, micelles, nanogels, nanoparticles, and fast-dissolving oral films are all critically examined. Mucoadhesion and amphiphilicity work together to enhance drug solubilization, regulate release, prolong mucosal retention, and promote transmucosal penetration. Research has demonstrated a three to five-fold increase in the bioavailability of drugs like ibuprofen, paclitaxel, curcumin, and melatonin. Translational aspects like pharmacokinetic performance, biocompatibility, green production, and regulatory acceptability are also discussed. All things considered, mucoadhesive-amphiphilic biopolymers provide a scalable and adaptable foundation for upcoming oral and buccal drug delivery systems designed to get around permeability and solubility limitations.