Development and Optimization of Doxycycline Hyclate and Aloe-Emodin NLC’s Loaded Gel for Diabetic Wound Healing

Chronic wounds in diabetic patients pose a significant healthcare challenge due to their slow healing rates and associated complications, which result in considerable morbidity, prolonged treatment durations, and elevated healthcare costs. This study aimed to optimize the doxycycline hyclate Aloe emodin-loaded nanostructured lipid carriers (DH-AE NLCs) approach and assess their therapeutic potential in diabetic wound healing. Different formulation variables were optimized to get the desired particle size, zeta potential, Polydispersity index (PDI), and entrapment efficiency. The diabetic wound healing potential of the formulated system was performed by In-vitro anti-microbial assay and in-vivo studies in rats and validated by histopathological analysis. The optimized formulation has a particle size of 165.32 nm, Zeta potential − 28.2, PDI 0.236, and entrapment efficiency of 79.99 %. X-ray diffraction and differential scanning calorimetry revealed that both APIs were amorphous in the DH-AE NLCs. In-vitro drug release studies showed a sustained release pattern over 24 h and followed the Higuchi model (R² = 0.98) release kinetics. The antimicrobial activity demonstrated significant inhibition against gram-positive and gram-negative bacteria. In-vivo anti-diabetic studies revealed a significant decrease in blood sugar levels in diabetic rats treated with the DH-AE NLCs formulation, achieving a 65% reduction after 14 days compared to 20% in the pure drug group. Histopathological analysis of skin tissues validated these findings, showing improvement in histopathological changes in damaged skin cells after treatment with gel. From the above findings, it concluded that the optimized DH-AE NLCs formulation has promising physicochemical stability, sustained drug release, enhanced antimicrobial activity, and found therapeutically effective in diabetic wound healing even more than the marketed formulation. Treatment with this gel will enable a path for the clinical society to achieve a synergistic therapeutic application in the management of diabetic wound healing.