Glycyrrhizic Acid-Loaded Poloxamer and HPMC-Based <i>In Situ</i> Forming Gel of Acacia Honey for Improved Wound Dressing: Formulation Optimization and Characterization for Wound Treatment

The present study aims to formulate a stimuli-responsive <i>in situ</i> hydrogel system to codeliver acacia honey and glycyrrhizic acid for topical application that will aid in absorbing wound exudates, control microbial infestation, and produce angiogenic and antioxidant effects to accelerate wound healing. Therefore, both the natural active constituents were incorporated within an <i>in situ</i> hydrogel composed of poloxamer and hydroxypropyl methylcellulose (HPMC), where the concentrations of the polymers were optimized using Design-Expert software considering optimum values of the dependent variables, gelation temperature (34-37 °C), gelation time (<10 min), and the viscosity (2000-3500 cPs). The optimized formulation showed improved physicochemical properties such as mucoadhesiveness, porosity, swelling, and spreadability, which makes it suitable for wound application. Additionally, the <i>in situ</i> hydrogel exhibited potent <i>in vitro</i> and <i>ex vivo</i> antioxidant effects, <i>in vitro</i> antimicrobial activities, and <i>ex ovo</i> angiogenic effects. Furthermore, the optimized formulation was found to be nontoxic while tested in the HaCaT cell line and acute dermal irritation and corrosion study. The findings of the <i>in vivo</i> wound-healing studies in experimental animal models showed complete wound closure within 15 days of treatment and accelerated development of the extracellular matrix. In addition, the antioxidant, antimicrobial, angiogenic, and wound-healing properties of acacia honey and glycyrrhizic acid coloaded <i>in situ</i> hydrogel were also found to be promising when compared to the standard treatments. Overall, it can be concluded that the optimized stimuli-responsive <i>in situ</i> hydrogel containing two natural compounds could be an alternative to existing topical formulations for acute wounds.