Potential Privilege of Maltodextrin-α-Tocopherol Nano-Micelles in Seizing Tacrolimus Renal Toxicity, Managing Rheumatoid Arthritis and Accelerating Bone Regeneration

Background: Tacrolimus (TAC) is a powerful immunosuppressive agent whose therapeutic applicability is confined owing to its systemic side effects. Objective: Herein, we harnessed a natural polymer based bioconjugate composed of maltodextrin and alpha-tocopherol (MD-alpha-TOC) to encapsulate TAC as an attempt to overcome its biological limitations while enhancing its therapeutic anti-rheumatic efficacy. Methods: The designed TAC loaded maltodextrin-alpha-tocopherol nano-micelles (TAC@MD-alpha-TOC) were assessed for their physical properties, safety, toxicological behavior, their ability to combat arthritis and assist bone/cartilage formation. Results: In vitro cell viability assay revealed enhanced safety profile of optimized TAC@MD-alpha-TOC with 1.6- to 2-fold increase in Vero cells viability compared with free TAC. Subacute toxicity study demonstrated a diminished nephro- and hepato-toxicity accompanied with optimized TAC@MD-alpha-TOC. TAC@MD-alpha-TOC also showed significantly enhanced anti-arthritic activity compared with free TAC, as reflected by improved clinical scores and decreased IL-6 and TNF-alpha levels in serum and synovial fluids. Unique bone formation criteria were proved with TAC@MD-alpha-TOC by elevated serum and synovial fluid levels of osteocalcin and osteopontin mRNA and proteins expression. Chondrogenic differentiation abilities of TAC@MD-alpha-TOC were proved by increased serum and synovial fluid levels of SOX9 mRNA and protein expression. Conclusion: Overall, our designed bioconjugate micelles offered an excellent approach for improved TAC safety profile with enhanced anti-arthritic activity and unique bone formation characteristics.

Automated summary

The designed bioconjugate micelles demonstrated improved safety profile of TAC with enhanced anti-arthritic activity and unique bone formation characteristics.