A multifunctional long‐term release system for treatment of hypothyroidism

Abstract

Hypothyroidism is an autoimmune disease associated with underactive thyroid gland. In this study, a dual effect polymeric system was designed to release Cepharanthine (CEP) to block T cell activation and Selenium (Se) to decrease the anti-thyroid peroxidase (TPOAb) concentration in order to treat hypothyroidism. For this purpose, poly(ethylenevinyl acetate) (PEVA) and polyethylene glycol (PEG) nanoparticles (NPs) including CEP were synthesized by emulsion solvent evaporation method and they were loaded to polyurethane (PU)/PEG-PUSe-PEG block copolymer blends which were fabricated by particulate leaching technique as porous sponges. Fourier-Transform Infrared (FTIR), Raman, and Nuclear Magnetic Resonance (NMR) analysis showed successful synthesis of PEG-PUSe-PEG block copolymer. A long-term zero-order release profile was obtained for CEP. Se release rate from matrices showed an oxidative stress-mediated release which can be used to adjust Se amount. According to MTS results conducted by NIH 3T3 fibroblasts, both NPs and matrices have no adverse effect on cell viability. Fluorescence microscopy and SEM images confirm the MTS results. The dual release system has potential to be effectively used in long-term treatment of hypothyroidism by addressing both auto-immune response and hormone regulation. K E Y W O R D SCepharanthine, controlled release system, hypothyroidism, selenium, thyroid hormones

Silicon Phthalocyanines as Anti‐infectious, Antioxidant, and Anticancer Agents

“…Cell Culture : The cells were obtained from American Type Culture Collection CCL‐221™, ATCC, USA). DMEM supplemented with 10 %FBS, 1 % L‐glutamine, and 1 % penicillin‐streptomycin was used as a culture medium [86] . Cells were incubated under normal conditions at 5 % CO 2 in a 37 °C humidified incubator in cell culture flasks.…”

“…DMEM supplemented with 10 % FBS, 1 % L-glutamine, and 1 % penicillin-streptomycin was used as a culture medium. [86] Cells were incubated under normal conditions at 5 % CO 2 in a 37 °C humidified incubator in cell culture flasks. High confluence cells detached with 0.5 % trypsin-EDTA solution and centrifuged at 350 × g for 5 minutes.…”

Promising Role of Alkaloids in the Prevention and Treatment of Thyroid Cancer and Autoimmune Thyroid Disease: A Comprehensive Review of the Current Evidence

“…Given these encouraging results, a dual effect polymeric system has been designed to treat, potentially, autoimmune hypothyroidism. The system involves the release of cepharanthine to block T cell activation and the release of selenium to decrease TPOAb levels [72]. Recently, cepharanthine has been revealed to block the binding of the TSH receptor peptide (TSHR.132) to HLA-DRβ1-Arg74 and, thus, to inhibit T-cell activation and cytokine response in a humanized, HLA-DR3 expressing, mouse model of Graves' disease [68].…”

Pharmacological Activity of Cepharanthine

“…Cepharanthine is effective in treating a range of autoimmune diseases, such as autoimmune thyroid disease, toxic diffuse goiter (Graves’ disease), Sjögren’s syndrome, and alopecia areata. Cepharanthine mainly treats autoimmune thyroiditis-related disorders [ 22 , 52 , 213 ], such as hypothyroidism, by blocking T-cell activation [ 213 ]. Cepharanthine is used to treat autoimmune thyroid disease by blocking T-cell activation through the thyroglobulin peptide Tg2098, a peptide that binds to the arginine-containing HLA-DR variant (DRβ1-Arg74) that causes autoimmune thyroid disease (AITD) [ 52 ].…”