Fractal features of dual temperature/pH-sensitive poly(N-isopropylacrylamide-co-acrylic acid) hydrogels and resultant effects on the controlled drug delivery performances

Using acrylic acid (AA) as pH-responsive monomer, and N-isopropyl acrylamide (NIPAM) as temperature-responsive monomer, the stimuli-responsive P(NIPAM- co -AA) copolymers were prepared via soap-free emulsion polymerization. Their constructed porous structures, swelling-shrinking behaviors, and controlled drug delivery performances were systematically demonstrated via various characterizations. Particularly, the small-angle X-ray scattering (SAXS) method was employed to elucidate their fractal features and the structural evolutions with increasing AA content, showing the occurrences from dense aggregates (mass fractal ( D m ) value of 2.92) to loose networks (surface fractal ( D s ) value of 2.18) with statistical self-similarity. Meanwhile, the ibuprofen (IBU) was used as a model drug, their temperature/pH-dual sensitive delivery and related mechanism were discussed on the basis of the fractal demonstrations. The results showed that the cross-linking networks with an interconnected open-cell skeleton and abundant large pores were beneficial to improve the adsorption-diffusion performances of the drug delivery, while the drug-releasing kinetics of P(NIPAM- co -AA)-30 followed a non-Fickian diffusion mechanism. Specially, the fractal evolutions of the obtained copolymers along with the drug loading and releasing behaviors were evaluated via SAXS patterns. In which, the drug-loaded copolymers presented the D s characteristics with the increased amounts of monomer AA added. While, the fractal features varied from D s value of 2.40 to D m value of 2.76 along with sustained drug releasing in pH 2.0 at 25 °C, indicating that the structural transformation of the used copolymers occurred from dense ( D m value of 2.86) to loose ( D m value of 2.76) with the extension of release time. These demonstrations suggested that the resultant P(NIPAM- co -AA) hydrogel is a potential intelligent-responsive drug carrier for targeted delivery.