Five TMC polymers with different degrees of quaternisation (12-59%) were synthesised and administered together with [14C]-mannitol in the nasal route of rats at a pH of 6.20 and 7.40, respectively. All the TMC polymers increased the nasal absorption of [14C]-mannitol significantly at pH 6.20, but only TMC polymers with higher degrees of quaternisation (>36%) were able to increase the absorption of this hydrophilic model compound at pH 7.40. The absorption of [14C]-mannitol at pH 7.40 increased with an increase in the degree of quaternisation of TMC until a maximum absorption value was reached with TMC with a degree of quaternisation of 48%. The absorption of [14C]-mannitol did not increase further, even when TMC with a higher degree of quaternisation (59%) was used. This can probably be explained by steric effects caused by the attached methyl groups and changes in the flexibility of the TMC molecules with an increase in the degree of quaternisation above an optimum value for absorption enhancement in a neutral environment. It was concluded that the degree of quaternisation of TMC plays an important role in the absorption enhancement properties of this polymer across nasal epithelia in a neutral environment.