Objective(s): Drug delivery via mucosal routes has been confirmed to be effective in inducing strong immune responses. Liposomes could enhance immune responses and mucoadhesive potentials, make them useful mucosal drug delivery systems. Coating of liposomes by mucoadhesive polymers succeeded in enhancing immune responses. Our studies aim at preparation and characterization of trimethylchitosan-coated nanoliposomes for nasal delivery of a model antigen, tetanus toxoid (TT).   Materials and Methods: Anionic liposomes were prepared by dehydration-rehydration method with an average size of 100 nm and were coated with 0.01% (w/v) solution of trimethyulchitosan (TMC) with 50±10% of quaternization. Surface properties and zeta potential were evaluated by DLS. Antigen stability and integrity were studied by SDS-PAGE electrophoresis. Nasal clearance rate and mucoadhesive properties of liposomes were studied by gamma scintigraphy method using 99mTc-labelled liposomes. Results: The zeta potential of non-coated and TMC-coated liposomes was -40 and +38.8, respectively. Encapsulation rate of tetanus toxoid was 77 ± 5.5%. SDS-PAGE revealed that the antigens remained intact during formulation procedure. Gamma scintigraphy confirmed that both types of liposomes could remain in nasal cavity up to ten folds over the normal residence time for conventional nasal formulations. Conclusion: TMC-coated nanoliposomes have several positive potentials including good mucoadhesive properties, preserved integrity of loaded antigen and presence of TMC as a mucoadhesive polymer with innate immunoadjuvant potential which make them suitable for efficient adjuvant/delivery system.