Optimizing Burn Wound Healing: The Critical Role of pH and Rheological Behavior in Plant-Derived Topical Formulations

<b>Background:</b> In burn injuries, wound healing effectiveness is complex and influenced significantly by the local biochemical environment and the physicochemical properties of topical preparations. pH lesions modulation can influence protection barrier integrity, inflammatory responses, and microbial colonization. Their antioxidant, antimicrobial, and anti-inflammatory properties, of the topical formulations enriched with plant extracts have demonstrated promising results. <b>Objective:</b> The aim of the study was to develop and characterize topical oleogel and hydrogel formulations containing ethanolic and hydroalcoholic extracts of medicinal plants (<i>Boswellia serrata</i>, <i>Ocimum basilicum</i>, <i>Sambucus nigra</i>, and <i>Galium verum</i>), and to evaluate the impact of their physicochemical properties, rheological behavior, in contrast with the wound pH modulation, and healing efficacy in an experimental burn model. <b>Methods:</b> Second-degree burns were induced uniformly on Wistar rats using the validated RAPID-3D device. All formulations were applied daily for 21 days, and wound healing was assessed through several measurements specific to the wound surface, skin temperature, pH, and, last but not least, histological analyses. Formulations' physicochemical and rheological properties, including pH, viscosity, and spreadability, were also analyzed and systematically characterized. <b>Results:</b> Oleogel formulations demonstrated superior wound healing performance compared to hydrogels. Formulations containing <i>Boswellia serrata</i> and <i>Ocimum basilicum</i> extracts significantly reduced wound size, inflammation, and melanin production by days 9 and 21 (<i>p</i> < 0.05). The beneficial outcomes correlated strongly with formulation acidity (pH < 6), high viscosity, and enhanced thixotropic behavior, indicating improved adherence and sustained bioactive compound release. Histological evaluations confirmed enhanced epithelialization and reduced inflammation. <b>Conclusions:</b> Particularly <i>Boswellia serrata</i> and <i>Ocimum basilicum</i> in oleogel formulations in ethanolic solvent effectively modulated wound pH, enhanced topical adherence, and improved burn wound healing. These findings highlight their potential clinical application and justify further clinical investigations.