Bio-inspired polyphenol-polyelectrolyte WRAP system for geometrically controlled AAV delivery in diverse anatomical...

Systemic delivery of therapeutics frequently requires elevated dosing to achieve effective local concentrations, often resulting in unintended toxicity and insufficient drug levels at the target site. To address this inherent limitation, localized drug and gene delivery strategies have been developed to deposit therapeutic payloads directly within diseased microenvironments. Herein, we report the development of a WRAP (Writable, Retentive, Adhesive, Permeable) drug delivery scaffold system, a biomaterial-mediated polyelectrolyte complex (PEC) film formed through spontaneous ionic complexation between chitosan and alginate. These naturally derived polymers form stable electrostatic interactions through their complementary charged groups, resulting in tunable film properties that maximize local therapeutic concentrations while minimizing adverse events during systemic exposure to therapeutics. To strengthen adhesion and sustain retention on wet tissue surfaces, chitosan-gallol (Chi-G) was incorporated as the cationic component of the PEC film, providing gallol-mediated surface binding and controlled loading of diverse therapeutic agents. When applied to adeno-associated virus (AAV), WRAP facilitated in situ viral retention, yielding significantly improved transgene delivery and prolonged transgene expression through improved spatial confinement. This enhanced spatial control represents a fundamental application of precision medicine principles, moving treatment beyond systemic toxicity toward highly efficient, site-specific interventions. Overall, WRAP functions as a versatile delivery platform that can be integrated with a range of therapeutic modalities requiring controlled, site-specific delivery.