الفهرس 
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Abstract
1-Vitamin E is one of the essential antioxidants whose limited aqueous solubility retracted its various applications.
Herein, we report the synthesis of tailored bio-conjugates composed of maltodextrin and vitamin E succinate at different degree of derivatization to address the poor solubility of vitamin E.
The identity of bioconjugates was characterized by FTIR and 1H NMR besides evaluation of antioxidant activity and in-vitro/in-vivo toxicological studies. Our findings displayed formation of new chemical entities with 4 folds increase in aqueous solubility compared to parent vitamin E succinate. Evaluation of the antioxidant activity using ABTS/DPPH scavenging assay was found to be dependent on degree of derivatization (DD) and revealed superior enhancement in antioxidant activity (” ” ” ” ” ” ” ” " ~ " ” ” ” ” ” ” ” ”80%) of the bioconjugates.
In vitro/in vivo bio-evaluations e.g. hemolysis, MTT assay and subacute toxicity study demonstrated the biological compatibility of bio-conjugates at specific ratios.
Moreover, histopathological inspection of liver and kidney showed no clear signs of cellular toxicity or inflammatory reaction. Overall, Maltodextrin-α-tocopherol bioconjugates represent new candidates of vitamin E with enhanced aqueous solubility and antioxidant activity and offer amphiphilic molecules to be employed as biocompatible carriers for different pharmaceutical applications
2- 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 α-tocopherol (MD-α-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-α-tocopherol nano-micelles (TAC@MD- α-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-α-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-α-TOC.
TAC@MD-α-TOC also showed significantly enhanced anti-arthritic activity compared with free TAC, as reflected by improved clinical scores and decreased IL-6 and TNF-α levels in serum and synovial fluids. Unique bone formation criteria were proved with TAC@MD-α-TOC by elevated serum and synovial fluid levels of osteocalcin and osteopontin mRNA and proteins expression. Chondrogenic differentiation abilities of TAC@MD-α-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.