Autoimmune diseases include a wide variety of diseases such as rheumatoid arthritis, osteoarthritis, and psoriasis. Rheumatoid arthritis (RA) is a chronic systemic disease that requires analgesic, anti-inflammatory (steroidal and non-steroidal), and joint tissue protection drugs to treat. In dealing with RA, the pain and inflammation should be removed in the early stages, and the destruction of the joint tissues should be prevented. For this purpose, in the first part of this thesis, a multifunctional core-shell nanocomposite with anti-inflammatory and tissue protection properties was designed. This nanocomposite was prepared using natural compounds with established therapeutic effects to achieve the highest medicinal potential with the lowest side effects. Then, nanocomposite core (TFH) was obtained by hydrothermal method using tragacanth and frankincense gums. Then, a layer of tannic acid-gold nanoparticles was immobilized as a shell on the hydrogel core (TFH@TA/AuNPs). Finally, 10-hydroxy-2-decanoic acid (10-HDA) was loaded within the nanocomposite structure (TFH@TA/AuNPs-HDA). TFH@TA/AuNPs-HDA nanocomposite was fully characterized in every step by different methods. The results showed that the nanocomposite particles are spherical and have a core-shell structure with a size of about 150-300 nm. Next, the water uptake capacity and biodegradability of TFH@TA/AuNPs-HDA were investigated. Also, the release profile of 10-HDA from the TFH@TA/AuNPs-HDA was determined using the spectrophotometer. The results showed that the release kinetics follows the Korsmeyer-Peppas model. Then, the biocompatibility of the nanocomposite was investigated. In addition, to investigate the efficiency and determine the mechanism of nanocomposite action, the interaction of 10-HDA and gold nanoparticles with the NF-κB inflammatory pathway components was investigated through molecular docking. The anti-inflammatory effect of TFH@TA/AuNPs-HDA was eva‎luated at mRNA and protein levels using real-time PCR and western blot methods. The results were consistent with the results of molecular docking and showed that TFH@TA/AuNPs-HDA nanocomposite can inhibit the NF-κB pathway and have anti-inflammatory potential. To complete the in vitro studies, the effect of TFH@TA/AuNPs-HDA was eva‎luated on rheumatoid arthritis rat models in vivo. Furthermore, inflammation is an important and complex complication in many autoimmune diseases. Hence, the amelioration of inflammation in the early stages as well as during the disease is very important. For this reason, in the second part of the current thesis, a new complex of ruthenium(III) and indigo ligand with the chemical formula Ru(HIndig)3 was synthesized and then loaded on the salep hydrogel which obtained in hydrothermal conditions. The prepared nanocomposite (SAH-Ru(HIndig)3) was characterized by different methods of microscopy, spectroscopy, elemental analysis, and thermogravimetry. The results showed that the nanocomposite has particles with a semi-spherical structure with a size of 120-250 nm. In addition, the water uptake capacity and biodegradability of SAH-Ru(HIndig)3 nanocomposite were investigated. Also, the release process of Ru(HIndig)3 complex from SAH-Ru(HIndig)3 nanocomposite is gradual and continuous and the release kinetics follows the Hixson-Crowell model.The anti-inflammatory effect of SAH-Ru(HIndig)3 was also investigated using the real-time PCR method and by determining the mRNA expression level of pro-inflammatory (TNF-α, IL-1β, and IL-6) and anti-inflammatory (IL-10) cytokines. Moreover, the results of the scratch assay showed that the SAH-Ru(Hindig)3 nanocomposite was affect the migration of macrophage cells. As a result, SAH-Ru(Hindig)3 nanocomposite can be used as an anti-inflammatory herbal-based compounds with minimal side effects.

علي حسين كيانفر , زهره ميراحمدي زارع

علي حسين كيانفر

فاطمه داور , علي حسين كيانفر , شهرام تنگستاني نژاد