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A self-assembled co-hydrogel system with sol-gel two-phase coexistence and mucoadhesive properties was developed based on the combined properties of fluoroalkyl double-ended poly(ethylene glycol) (R f -PEG-R f ) and poly(acrylic acid) (PAA), respectively. We have synthesized an R f -PEG-g-PAA (where g denotes grafted) copolymer and integrated it into the R f -PEG-R f physically cross-linked micellar network to form a co-hydrogel system. Tensile strengths between the co-hydrogel surfaces and two different sets of mucosal surfaces were acquired. One mucosal surface was made of porcine stomach mucin Type II, while the other one is a pig small intestine. The experimental results show that the largest maximum detachment stresses (MDSs) were obtained when the R f -PEG-g-PAA's weight percent in the dehydrated polymer mixture is ~15%. Tensile experiments also found that MDSs are greater in acidic conditions (pH = 4-5) (123.3 g/cm 2 for the artificial mucus, and 43.0 g/cm 2 for pig small intestine) and basic conditions (pH = 10.6) (126.9 g/cm 2 , and 44.6 g.cm 2 , respectively) than in neutral pH (45.4 g/cm 2 , and 30.7 g.cm 2 , respectively). Results of the rheological analyses using shear strain amplitude sweep and frequency sweep reveal that the R f -PEG-g-PAA was physically integrated into the R f -PEG-R f micellar network, and the co-hydrogels remain physically cross-linked in three-dimensional micellar networks with long-term physical dispersion stability. Therefore, the co-hydrogel system is promising for drug delivery applications on mucosal surfaces.

Mucoadhesive and Rheological Studies on the Co-Hydrogel Systems of Poly(Ethylene Glycol) Copolymers with Fluoroalkyl and Poly(Acrylic Acid)