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The potentials held by stimuli-responsive polymers in wound dressing have led to the present research in formulating a hydrogel base formulation with polymers having pH and thermo-sensitivity. Thus, hyaluronic acid (pH-sensitive polymer), and Pluronic F-127 (thermo-sensitive polymer) with hydroxypropyl methylcellulose (mucoadhesive polymer) were incorporated to obtain an  in situ  hydrogel containing gentamicin and naringenin (NAR). The optimization of the stimuli-responsive formulation was performed by the Box–Behnken statistical design to acquire variable parameters that influence the gelling temperature and viscosity. Thermo-gravimetric analysis, differential scanning calorimetry, and Fourier-transform infrared spectroscopy were performed to confirm the suitability of incorporating the selected polymers with drugs. The optimized formulations (blank and drug-loaded) were found to possess satisfactory characteristics of gelling temperatures (30–33°C), viscosities (174 ± 3 to 184 ± 4 cP), and mucoadhesive properties (0.29 ± 0.01 to 0.31 ± 0.01 N) with a spray diameter of 16.8 ± 1.4 to 18.9 ± 1.2 cm 2  to facilitate the application at the wound environment. The  in vitro  drug release study depicted a sustained release profile over a time frame of 8 h with a cumulative release of 56.18 ± 4.59% NAR. The drug-containing  in situ  hydrogels showed superior potency by producing a larger zone of inhibition (2.03 ± 0.12 cm). Furthermore, a cytotoxicity study of the developed formulations in HaCaT cells revealed no toxicity of the drug-loaded formulations when compared to the blank hydrogel. These findings indicate the potential of the  in situ  hydrogel as an effective wound dressing for chronic wounds; however, additional investigation is needed for further implementation.

A stimuli-responsive in situ spray hydrogel co-loaded with naringenin and gentamicin for chronic wounds