Nano-medicine can passively accumulate in chronic inflammatory tissues via the enhanced permeability and retention phenomenon, or by being conjugated with a ligand that can bind to receptors over expressed by cells inside chronic inflammatory tissues, contributing to reduced systemic side-effects and increased efficacy. This article highlights the utilization of nanomedicine for potential treatment of rheumatoid arthritis. Rheumatoid arthritis was induced in rat model via 2 weeks intradermal injection of pristane at the base of the tail in a daily dose of 150 μl. Susceptible rat strains developed severe arthritis with a sudden onset 3 weeks post pristane injection. Three weeks post pristane administration; rats were treated intravenously with glutathione or liposomal-glutathione in a dose of 5 mg/kg daily for 30 days. Concomitant supplementation with the aforementioned antioxidants effect on proinflammatory marker C-reactive protein (CRP) was assessed. On the other hand, oxidative stress biomarker malondialdehyde (MDA) and rheumatoid factor (RF) compared with pristane treated group was also investigated. The results elucidated that glutathione and liposomal -glutathione significantly reduced rheumatoid factor, malondialdehyde and C-reactive protein levels with the superiority of liposomal -glutathione in this side reflecting its pronounced effect as anti-rheumatoid agent.

Methotrexate (MX), a competitive inhibitor of dihydrofolate reductase, can inhibit DNA and RNA production and is a powerful anticancer agent widely utilized in clinical practice for treating nonneoplastic maladies, as psoriasis and rheumatoid arthritis; meanwhile, its probable prescription dose and interval of administration are strictly limited due to dose-related organ damage. Former studies verified that kidney, brain, liver, and lung harms are prospective obstacles of methotrexate administration. To understand the machinery of methotrexate-prompt toxicity, various mechanisms were investigated. The former is an autophagy defense mechanism; autophagy is a self-digesting mechanism responsible for the removal of damaged organelles and malformed proteins by lysosome. The contemporary article hypothesized that turmeric or its liposomal analog could defeat autophagy of MX-induced acute toxicity. Methotrexate, in a dose of 1.5 mg/kg, was administered intravenously followed by turmeric and liposomal turmeric treatment in a dose of 5 mg/kg for 30 days in rats. Increment in autophagy (AUTP) consent by MX administration was attenuated by concurrent treatment via turmeric and liposomal turmeric that was reliable on the alteration in apoptotic markers. The assembly of FOXO-3 in serum post methotrexate administration was suppressed by concurrent treatment via liposomal turmeric. Apoptosis/autophagic marker investigation was evaluated through the gene expression of Bax (BCL2-associated X protein)/Bcl2 (B-cell lymphoma 2)/P53 (tumor protein P53)/SiRT-1 (sirtuin silent mating-type information regulation 2 homolog 1) and FOXO-3 (forkhead box transcription factor-3)/ERDJ-4 (endoplasmic reticulum localized DnaJ homologs)/BNP (brain natriuretic peptide B) signaling. The cell death of all cells was categorized to achieve autophagy. Interestingly, Bax/Bcl2/P53/SiRT-1 signaling pathways were downregulated, contributing to inhibiting the initiation of autophagy. Meanwhile, FOXO-3/BNP/ERDJ-4 reduction-implicated noncanonical autophagy pathways were involved in methotrexate-induced autophagy, whereas this change was suppressed when turmeric was administered in liposomal form. These outcomes recommended that liposomal turmeric prevents MX-induced acute toxicity through its autophagy, antioxidant, and antiapoptotic properties.