Investigating the Selective Toxicity of Iron-Loaded Curcumin Nanoparticles on Fibroblast Cells Isolated from the Skin of an Animal Model of Diabetic Foot Ulcer

Background &

In the world, every 20 seconds, a patient loses his leg due to diabetes. it is also known that diabetic foot ulcers develop in the feet of about 300,000 patients every year, and it is known that 20,000-30,000 of these patients lose their legs. The increasing prevalence of diabetes worldwide has caused countless personal and social problems. So that today this disease has become an epidemic. Diabetic foot ulcer is a common disease among patients with type 1 and 2 diabetes, which is usually caused by an injury, even if minor, to the feet. The treatment of these wounds in people who do not have diabetes is usually done spontaneously, but in the case of diabetic patients, it is necessary to take care of this wound quickly and pay attention to it to avoid possible risks and problems. Peripheral neuropathy and lower limb ischemia caused by peripheral artery disease are considered to be the main causes of diabetic foot ulcer. Diabetic peripheral neuropathy is one of the accelerating factors in almost 90% of diabetic foot ulcers. This wound is usually formed under the ankle as a result of a break in the skin structure and gradually involves the lower layers of the skin. It is one of the health and economic-social problems. This complication is the main cause of disability and incurs high costs for diabetic patients. Also, infections at the time of diabetic foot ulcer is another problem of sufferers, that's why researchers are trying to use different scientific fields for the best result in improving the damage caused by diabetic foot ulcer. Curcumin, the biologically active substance of turmeric, has wide biological properties, such as anti-inflammatory, antioxidant, anti-diabetic and anti-cancer. Although due to the low solubility of this substance in water, the use of its medicinal and biological properties is limited, but despite its limited availability in the level of biological activity, curcumin has shown positive and noticeable effects in the human digestive system and the body's defense systems. It inhibits various types of diseases. The effective ability of inhibiting the stringing of various proteins in the condition of fibrillation and also inhibiting the production of reactive oxygen species by this molecule have been studied. Curcumin regulates their function by reacting directly or indirectly with more than 30 proteins. The low dissolution of curcumin in water causes its use to be limited. For this reason, many studies have been done to increase its dissolution. Curcumin encapsulation using some carrier molecules, such as bovine serum albumin, increases the effectiveness of curcumin. Betacasein is among the proteins that can create nanostructured micelles that act as a carrier for hydrophobic molecules. In a study, our research group used beta-caseins from camel milk to encapsulate curcumin, the results of which show an increase in the solubility of curcumin up to 2400 times, and to improve the performance of curcumin, today researchers have been able to create nanoparticle structures of this composition. In recent years, studies in the field of nanoparticles are being carried out at a high speed. The scope of nanomedicine includes pharmaceutical applications and nanoelectronic and nanomolecular biosensors. Nanomedicine can have a significant impact on life-threatening diseases. The diseases that can be affected by nanotechnology in the next few years include cancer, diseases of the cardiovascular system, lungs, blood, brain and nerves, diabetes, inflammatory/infectious diseases, and Parkinson's disease or Alzheimer's and orthopedic problems. In recent years, researchers have investigated and scientifically studied various factors such as particle size, nanoparticle morphology, material type selection, and nanomaterial synthesis and optimization techniques to provide an ideal nanosystem for targeted and more effective drug delivery. The diverse properties of nanoparticles have made it possible to provide understandable and reassuring solutions for therapeutic, diagnostic, preventive and biological challenges in the field of nanomedicine research. However, the challenges of the physiological system are very complex and the cells show various responses at the nanoscale level, so understanding the interaction of nanomaterials and biological compounds and nanobiotechnological studies are very necessary and important. Macromolecular synthesis and polymer diversity have found wide applications in therapeutic applications. Nanocomposites and nanoparticles are used in the fields of inducing the growth of cells and also in the delivery of drugs to the target tissue. It has also been shown in cell studies that damage to the cell activates a huge amount of oxidative stress, which has irreparable effects on the systems and organs of living organisms.

We designed superparamagnetic iron oxide nanoparticles loaded with curcumin (Fe3O4 magnetic- CurNPs) to achieve an enhanced co-therapeutic effect. The physicochemical properties of Fe3O4 magnetic- CurNPs were characterized using X-ray diffraction (XRD), and dynamic laser light scattering (DLS) and zeta potential. Further, to prove Fe3O4 magnetic-CurNPs results in superior therapeutic effects, and also, the cell viability, reactive oxygen species production (ROS), lipid peroxidation level, cytochrome c release, as well as histopathological changes in skin tissue.

We showed that effective co-treatment with nanoparticle induced oxidative stress and mitochondrial dysfunction in the diabetic foot ulcer. Nanoparticle, as well as cell viability low level reduced in the cells of treated group compared with control (p < 0.05). ROS generation, lipid peroxidation and cytochrome c release were (p < 0.05) increased in the cells of treated group compared with control group.

Taken together, Fe3O4 magnetic-CurNPs exhibits potent antioxidant activity in fibroblast isolated from skin diabetic foot ulcer. This approach can be extended to preclinical use in skin foot ulcer treatment in the future.