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

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/cm² for the artificial mucus, and 43.0 g/cm² for pig small intestine) and basic conditions (pH = 10.6) (126.9 g/cm², and 44.6 g.cm², respectively) than in neutral pH (45.4 g/cm², and 30.7 g.cm², 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.