Curcumin delivery systems as dressing components for the treatment of diabetic foot ulcers: test on macrophages polarization

The natural wound healing process consists of four basic phases: homeostasis, inflammation, proliferation, and remodelling. Macrophages play an important role in the body’s response to biomaterials, as they are modulators of the wound healing process and can polarize into different phenotypes capable of inducing both deleterious and beneficial effects on tissue repair. Curcumin (CU) is known for its anti-inflammatory properties and has the potential to treat diabetic foot ulcers, but it should be delivered to wounds in a controlled manner. In this study, the encapsulation of curcumin in polymeric microparticles based on poly(sebacic anhydride) (PSA) was developed using an emulsification method. PSA-based microparticles containing different concentrations of CU were obtained: 0% weight (wt). CU (unloaded microparticles), 5, 10, and 20 wt% CU. CU encapsulation efficiency and loading were determined using a fluorescence-based calibration curve method and semi-quantitative Fourier-transform infrared spectroscopy (FTIR) analysis. The potential cytotoxicity of the obtained biomaterials in contact with primary human macrophages and their susceptibility to polarization from the M1 (pro-inflammatory) phenotype to the M2 (antiinflammatory) phenotype were evaluated. The morphology of cells cultured in contact with polymeric microparticles was evaluated using phalloidin red and 4′,6-diamidino2-phenylindole (DAPI) staining. Macrophage phenotype was assessed using flow cytometry. The obtained biomaterials showed no cytotoxic effect on primary human macrophages. Flow cytometry studies showed enhanced polarization of macrophages into anti-inflammatory M2 phenotype when exposed to microparticles loaded with CU and CU powder as compared to unloaded microparticles