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Localized delivery of chemotherapeutic agents allows extended drug exposure at the target site, thereby reducing systemic toxicity. We report the development of functionalized polymeric patch with unidirectional drug release to treat gastric cancer. The oxaliplatin-loaded patch was prepared by incorporating sodium carboxymethyl cellulose, hydroxypropyl cellulose and polyvinylpyrrolidone. The patch was functionalized by coating with transferrin-poly(lactic-co-glycolic acid) conjugate on one side of the patch for cancer targeting. The other side of the patch was coated with ethylcellulose (EC) to restrict the release of oxaliplatin. The physical and mechanical properties of oxaliplatin-loaded patches were characterized. Mucoadhesion studies using excised rat stomach tissue have shown that the functionalized side of the patch has significantly (p < 0.05) greater mucoadhesion strength compared with EC coated side of the patch. The in vitro and ex vivo (stomach sac and open-membrane model) studies revealed greater permeation of oxaliplatin across the stomach tissue when adhered to the functionalized and non-functionalized side of the patch compared with EC coated side. It was found that the growth inhibition with oxaliplatin solution was not significantly greater compared with corresponding concentrations of oxaliplatin-loaded patch in AGS and Caco-2 cell models. The in vivo studies were performed in mice, where indocyanine green-loaded patch encapsulated in a gelatin capsule was orally administered. The near-infrared (NIR) optical imaging revealed adherence of the patch on the mucosal side of the stomach tissue for up to 6 h. In conclusion, the functionalized polymeric patch loaded with oxaliplatin can be a potential localized delivery system to target gastric cancer., (Copyright © 2021 Elsevier B.V. All rights reserved.)