To explore the correlations between mucoadhesion and the surface properties of mucoadhesive polymers, a series of polymer, poly[acrylic acid-co-poly(ethylene glycol) monomethylether monomethacrylate-co-dimethy-laminoethyl methacrylate], poly(AA-PEGMM-DMEMA), was designed and synthesized as a model mucoadhesive in this study. Poly(AA-PEGMM-DMEMA) was prepared by free radical polymerization. The composition of the polymer was varied by changing the content of DMEMA from 0 to 2.9 mol %, while keeping the mole ratio of AA to PEGMM at constant 9:1. The contact angles of water, glycerol (GL), or diiodomethane (DIM) on the surface of polymers with different hydration levels were measured, respectively. Surface energy components of the Lifshitz-van der Waals and the Lewis acid-base interactions for the polymer were calculated, based on the measured contact angles of water, GL, and DIM. The free energy of mucoadhesion (AG) of the polymer on the buccal surface was estimated by interfacial free energy of a ternary system, consisting of mucin, polymer, and normal saline. The mucoadhesion of the polymer was measured after prehydration for 0, 5, and 180 min. It was found that Lewis acid-base interactions and Lifshitz-van der Waals interactions played different roles in the process of mucoadhesion. Increasing Lewis acid-base interaction between the polymer and the buccal mucosa led to a thermodynamically favorable adhesion process. Hydration could greatly affect mucoadhesion by changing the thermodynamic properties of the surface. Restricted hydration promoted the formation of mucoadhesive joints. The force of mucoadhesion was correlated mathematically with the effects of various interactions involved in the process of mucoadhesion. (c) 2006 Wiley Periodicals, Inc.