Abstract
BACKGROUND AND OBJECTIVES: Targeting macro-autophagy (MAut) through Nano-medicine can be more prospective than traditional medicine subjected to resistance in atrophic arthritis (RA). MAut is a degenerative process that restores healthy chondrocytes it plays a vital role in RA onset and cell homeostasis this opened Novel Avenue in targeting RA via liposomal drug delivery system. The insufficient response to existing therapies or systemic toxicity and poor bioavailability, are quiet unsettled problems lying across the full retardation of RA treatment. Various Nano-carriers with sustained drug release, improved physicochemical properties, and active targeting were designed to promote the drug delivery efficiency. METHODS: Single subcutaneous dose of Norphytane (200 μL) induced Atrophic arthritis in rat model then rats were treated with Liposomal loaded-Isethione or Isethione. RESULTS: Liposomal-Isethione ameliorated autophagy biomarkers including Beclin-1, P62, and X-box binding protein-1 (XBP-1), cell survival, and oncogenic biomarkers including Signal transducer and activator of transcription (STAT-3A), Phosphoinisitol kinase-3 (PI3K), AKT Serine/Threonine Kinase-1 (AKT), and Phosphatase and tensin homolog (PTEN) post elevation via Norphytane. Moreover, rheumatoid factor biomarkers including Cartilage oligomeric matrix protein (COMP), matrix metalloproteinase (MMP-9), tumor necrosis factor (TNF-α). CONCLUSION: Liposomal-Isethione significantly targeted MAut signaling pathways, including Beclin-1/XBP/COMP/STAT-3A/PI3K/AKT/PTEN via increased bioavailability and targeting inflamed tissues, thus decreased drug resistance.