Development of a thermosensitive enrofloxacin hydrogel suspension for intrauterine infusion in cattle.

Bovine endometritis is a major reproductive disorder in cattle that reduces fertility, prolongs calving intervals, and decreases productivity in the livestock industry. However, limitations in current therapeutic approaches underscore the need for novel and more effective therapeutic formulations. This study aimed to develop an enrofloxacin suspension-based thermosensitive hydrogel intrauterine infusion (Enro-TSH). We utilized 16% Poloxamer 407 and 0.5% Poloxamer 188 as the gel matrix and Carbopol 941 as the suspending agent. We screened formulations with Carbopol 941 contents of 0.00%-0.14% by characterizing their rheological properties, sedimentation volume ratio, in vitro release profiles and microstructures, and identified 0.08% as the optimal Carbopol concentration. The optimally screened formulation Enro-TSH-Car8 showed viscosities (η) of 6.04 ± 0.59 Pa·s at 4°C, 7.22 ± 0.31 Pa·s at 25°C, and 785 ± 42.46 Pa·s at 38.5°C, with a gelation temperature of 35.60 ± 0.75°C and gelation time of 123 ± 8 s. We then conducted in vitro release studies using 0.9% sodium chloride solution as the medium, and obtained cumulative release rates of 48.73 ± 2.61% at 12 h and 94.1 ± 3.89% at 24 h. Specifically, the cumulative release profile from 1 to 24 h closely fitted a zero-order kinetic equation (R 2 = 0.991). Drug release from 1 to 6 h adhered to the Ritger-Peppas model (R 2 = 0.992, n > 0.89), indicating a matrix erosion mechanism, whereas release from 6 to 24 h complied with the Higuchi model (R 2 = 0.999), suggesting a diffusion-driven mechanism. In addition, we characterized the freeze-dried formulation via scanning electron microscopy (SEM), and neither enrofloxacin nor Carbopol significantly affected the gel microstructure. Overall, this study successfully developed a thermosensitive intrauterine infusion loaded with suspended enrofloxacin particles for bovine endometritis. This novel integrated system unites thermo-responsive hydrogel and suspension formulation, adopting the lowest reported Poloxamer 407 content (16%) and an optimized Carbopol concentration to balance suspension stability and rheological properties. Meanwhile, the enrofloxacin-loaded formulation exhibits a mild pH value (7.0 ± 0.2), providing a promising strategy for the treatment of bovine endometritis.