A stimuli-responsive <i>in situ</i> spray hydrogel co-loaded with naringenin and gentamicin for chronic wounds
Thaneswary Thangarajoo, Yong Kai Hsin, Manisha Pandey, Hira Choudhury, Lim Wei Meng, Shadab Md, Md Habban Akhter, Bapi Gorain
Abstract
Abstract 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.