Ultradeformable liposomes for mucosal delivery: exploring oral, nasal, and vaginal routes

Abstract

While originally developed for topical cutaneous delivery, ultradeformable liposomes (UDLs) have recently emerged as versatile platforms for mucosal drug administration. These nanometric carriers, also known as transfersomes, are distinguished by an exceptional membrane elasticity conferred by edge activators, which allows them to outperform conventional rigid vesicles. This review compiles and critically analyzes UDL applications across oral (buccal and sublingual), nasal, and vaginal routes, highlighting their capacity to enable active, structure-driven penetration through non-keratinized stratified epithelia. Key findings demonstrate that UDLs can access deeper tissue compartments, penetrate dense antimicrobial biofilms, and even facilitate nose-to-brain transport. However, despite these encouraging preclinical outcomes, clinical translation remains limited by challenges in industrial scalability, long-term stability, and regulatory hurdles. By summarizing the current state of UDL-mediated mucosal delivery, this article outlines their therapeutic potential while identifying the critical barriers that must be addressed for successful clinical implementation.