Nanocarrier mediated formulations of tetrahydrocurcumin and folic acid for diabetic foot ulcer

Abstract

Diabetic foot ulcers are a significant healthcare problem that highly impacts the quality of life. Several treatment options have been explored to accelerate wound healing. The present investigation aimed to develop a novel dissolvable patch of nanolipidic carriers of tetrahydrocurcumin (THC) and folic acid (FA) for ulcer healing (Patent application no. 202211045937 A). The synergistic effects of these combinations were evaluated in in-vitro and in-vivo models. A Taguchi screening and Box-Behnken optimization design with three factors and three levels were used to optimize the preparation of THC-FA-NLCs. The resulting NLCs had a mean particle size of 125±6 nm, PDI of 0.22±0.4, zeta potential of -22±2 mV, and demonstrated remarkable stability over six months. Dissolvable patches of THC-FA-NLCs (THC-FA-NLCs-DP) were prepared using the solvent casting method. The patches were uniform in weight, thickness, and drug content, and were non-toxic to human dermal fibroblast (HDF) cells, causing no hemolysis. In-vitro cytocompatibility on HDF cells, confocal microscopy, and flow cytometry indicated enhanced internalization of NLCs in specific cells, with clathrin- mediated pathways identified as the predominant mode of internalization. The optimized NLCs significantly reduced inflammatory markers (IL-6 and TNF-and#945;) compared to the untreated diabetic control. In-vivostudies on a diabetic rat model demonstrated that the optimized THC-FA-NLCs exhibited superior wound closure, and collagen deposition compared to THC and FA alone. Biochemical assays also showed a significant increase in protein levels. In conclusion, THC-FA-NLCs-DP is expected to open new avenues in the treatment of DFU. newline