Osthole‐Laden Lyotropic Liquid Crystalline Nanoparticle‐Impregnated Cryogel for Diabetic Wound Healing: QbD Optimization, In silico and In Vitro Evaluation

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ABSTRACT Osthole (OS), a natural coumarin derivative with anti‐diabetic, antioxidant, and anti‐inflammatory properties, shows promise for diabetic wound healing. Preliminary molecular docking studies demonstrated moderate binding affinities of OS toward MMP‐9, Keap‐1, and TLR‐4, indicating its potential to modulate key wound‐healing biomarkers. However, the poor aqueous solubility of OS limits its therapeutic efficacy. To overcome this limitation, OS was encapsulated into lyotropic liquid crystalline nanoparticles (OS‐LLCNPs) and optimized using a central composite design. The optimized formulation exhibited a particle size of 168.5 ± 1.13 nm, PDI of 0.1973 ± 0.03, zeta potential of −16.09 ± 2.14 mV, encapsulation efficiency of 89.42 ± 4.27%, and drug loading of 1.51 ± 0.2%. FT‐IR analysis confirmed successful encapsulation and compatibility of formulation components. In vitro release studies showed approximately 90% cumulative drug release within 24 h. Cell culture studies demonstrated good cytocompatibility under normal and glucose‐induced diabetic conditions, while OS‐LLCNPs significantly enhanced fibroblast migration (6.51‐fold increase). Incorporation of OS‐LLCNPs into a cryo‐gel produced a porous, shear‐thinning matrix with favorable moisture‐handling and degradation properties, supporting its potential as a promising platform for diabetic wound healing.

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