Engineering a Nanostructured Hybrid Gel System with Sodium Humate for Enhanced Wound Healing

The development of effective topical drug delivery systems remains a key challenge in wound management, particularly for bioactive compounds with limited skin permeability. In this study, a nanostructured bigel system incorporating sodium humate-loaded ultra-deformable vesicles (UDVs) was developed and evaluated for wound healing applications. Sodium humate-loaded UDVs were prepared using a thin-layer hydration method, and the influence of key technological parameters (phospholipid/glycerol concentrations, sonication time) on vesicle size and encapsulation efficiency was investigated. An optimized UDV formulation characterized by small particle size, high stability, and high drug encapsulation efficiency was selected and incorporated into a bigel composed of hydroxypropyl methylcellulose hydrogel and andiroba oil oleogel. The developed bigels were characterized in terms of microstructure, physical stability, pH, spreadability, and rheological behavior, demonstrating suitable properties for dermal application. In vivo wound healing evaluation in rat wound models revealed that bigels containing sodium humate-loaded UDVs significantly enhanced wound closure and tissue regeneration compared to control and reference treatments. Histopathological analysis confirmed improved granulation tissue formation and complete epithelialization. Overall, the results demonstrate that the proposed UDV-loaded hybrid bigel represents a promising nanostructured platform for enhanced dermal delivery and wound healing therapy.