Pullulan dialdehyde cross-linked dual-action adhesive with high adhesion to lung tissue and the capability of...

To address the main challenges for thoracoscopic lung cancer surgery, including persistent pulmonary air leaks and cancer recurrence, this study developed an in-situ adhesive that can effectively adhere to the lung and release the anticancer drug in response to pH. The adhesive was formulated using hydrophobically modified cold-water fish skin gelatin (hm-CFG) and cross-linking agent pullulan dialdehyde (PDA), in which succinic dihydrazide-modified doxorubicin (SDH-DOX) can be incorporated. Utilizing PDA could improve both cohesion and interfacial adhesion, while also offering drug-loading sites through the aldehyde groups that were not involved in cross-linking. The optimal adhesive formulation was 9C10-CFG/PDA (30 w/v% 9 mol% decanal modified CFG/20 w/v% PDA). The 9C10-CFG/PDA adhesive exhibited suitable cohesive strength, good mechanical flexibility (tensile strain over 170 %), and strong interface adhesion. The burst strength of 9C10-CFG/PDA adhesive (131.5 ± 22.2 mm Hg) was almost 6-fold higher than that of commercial fibrin sealant. In a rat pneumothorax model, 9C10-CFG/PDA adhesive displayed favorable wound-sealing properties, as evidenced by CT imaging and restored rat behavior. When combined with the anticancer drug, SDH-DOX@Adhesive could release the drug in response to pH more gradually than DOX@Adhesive. This dual-action adhesive is anticipated to mitigate post-surgical occurrences of lung air leaks and cancer recurrence.