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

[Display omitted] •P(NIPAM-co-AA) copolymer with dual temperature/pH- responsive property was prepared.•Structural irregularity and surface roughness of copolymer were evaluated via SAXS data.•IBU-releasing mechanism from P(NIPAM-co-AA) was proposed from fractal perspective.•Fractal evolutions of P(NIPAM-co-AA) were elucidated in the drug delivery process. 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 (Dm) value of 2.92) to loose networks (surface fractal (Ds) 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 Ds characteristics with the increased amounts of monomer AA added. While, the fractal features varied from Ds value of 2.40 to Dm 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 (Dm value of 2.86) to loose (Dm 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.