Aileen Weide, Friederike Brokmann, Bettina Appel, Christoph Rosenbaum, Julius Krause, Una Janke, Mihaela Delcea, Werner Weitschies, Sabine Müller

• The development of RNA and oligonucleotide‐based therapeutics is a longstanding goal and is currently gaining significant attention. Several RNA‐based drugs are approved for clinical use. Others are under investigation or in preclinical trials. This study have initiated the development of RNA drugs for localized use in the esophagus, utilizing the EsoCap System. This system's core component is a mucoadhesive film that carries the RNA drug and is precisely applied to the esophagus. Research into the stability and properties of naked and liposomal‐encapsulated RNA on mucoadhesive polymer film reveals that RNAs remain stable in various conditions without degradation, RNA leakage, or liposome fusion observed. The liposome size also remains constant after application on the film, drying, and rehydration. These findings pave the way for RNA drug development for esophageal diseases and their administration via the EsoCap system.