Potential Privilege of Maltodextrin-α-Tocopherol Nano-Micelles in Seizing Tacrolimus Renal Toxicity, Managing Rheumatoid Arthritis and Accelerating Bone Regeneration
Hala M Helal,1 Wael M Samy,1 Elbadawy A Kamoun,2,3 Esmail M El-Fakharany,4 Doaa A Abdelmonsif,5,6 Rania G Aly,7 Sana M Mortada,1 Marwa A Sallam1 1Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt; 2Polymeric Materials Research Dep., Advanced Tech...
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Dove Medical Press
2021
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polymeric micelles vitamin e osteopontin sox9 rheumatoid Medicine (General) R5-920 |
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polymeric micelles vitamin e osteopontin sox9 rheumatoid Medicine (General) R5-920 Helal HM Samy WM Kamoun EA El-Fakharany EM Abdelmonsif DA Aly RG Mortada SM Sallam MA Potential Privilege of Maltodextrin-α-Tocopherol Nano-Micelles in Seizing Tacrolimus Renal Toxicity, Managing Rheumatoid Arthritis and Accelerating Bone Regeneration |
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Hala M Helal,1 Wael M Samy,1 Elbadawy A Kamoun,2,3 Esmail M El-Fakharany,4 Doaa A Abdelmonsif,5,6 Rania G Aly,7 Sana M Mortada,1 Marwa A Sallam1 1Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt; 2Polymeric Materials Research Dep., Advanced Technology and New Materials Research Institute (ATNMRI), City of Scientific Research and Technological Applications (SRTA-City), New Borg Al-Arab City, Alexandria, 21934, Egypt; 3Nanotechnology Research Center (NTRC), The British University in Egypt (BUE), El- Sherouk City, Cairo, 11837, Egypt; 4Proteins Research Dep., Genetic Engineering and Biotechnology Research Institute (GEBRI), City of Scientific Research and Technological Applications (SRTA-City), New Borg Al-Arab City, Alexandria, 21934, Egypt; 5Department of Medical Biochemistry, Faculty of Medicine, Alexandria University, Alexandria, 21521, Egypt; 6Center of Excellence for Research in Regenerative Medicine and Applications (CERRMA), Faculty of Medicine, Alexandria University, Alexandria, 21521, Egypt; 7Department of Surgical Pathology, Faculty of Medicine, Alexandria University, Alexandria, 21521, EgyptCorrespondence: Marwa A SallamDepartment of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, EgyptTel +20 3 4868256Fax +20 3 4871668Email marwa.sallam@alexu.edu.egElbadawy A KamounPolymeric Materials Research Dep., Advanced Technology and New Materials Research Institute (ATNMRI), City of Scientific Research and Technological Applications (SRTA-City), New Borg Al-Arab City, Alexandria, 21934, EgyptTel +20 1283320302Email e-b.kamoun@tu-bs.deBackground: 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.Keywords: polymeric micelles, vitamin E, osteopontin, SOX9, rheumatoid |
| format |
article |
| author |
Helal HM Samy WM Kamoun EA El-Fakharany EM Abdelmonsif DA Aly RG Mortada SM Sallam MA |
| author_facet |
Helal HM Samy WM Kamoun EA El-Fakharany EM Abdelmonsif DA Aly RG Mortada SM Sallam MA |
| author_sort |
Helal HM |
| title |
Potential Privilege of Maltodextrin-α-Tocopherol Nano-Micelles in Seizing Tacrolimus Renal Toxicity, Managing Rheumatoid Arthritis and Accelerating Bone Regeneration |
| title_short |
Potential Privilege of Maltodextrin-α-Tocopherol Nano-Micelles in Seizing Tacrolimus Renal Toxicity, Managing Rheumatoid Arthritis and Accelerating Bone Regeneration |
| title_full |
Potential Privilege of Maltodextrin-α-Tocopherol Nano-Micelles in Seizing Tacrolimus Renal Toxicity, Managing Rheumatoid Arthritis and Accelerating Bone Regeneration |
| title_fullStr |
Potential Privilege of Maltodextrin-α-Tocopherol Nano-Micelles in Seizing Tacrolimus Renal Toxicity, Managing Rheumatoid Arthritis and Accelerating Bone Regeneration |
| title_full_unstemmed |
Potential Privilege of Maltodextrin-α-Tocopherol Nano-Micelles in Seizing Tacrolimus Renal Toxicity, Managing Rheumatoid Arthritis and Accelerating Bone Regeneration |
| title_sort |
potential privilege of maltodextrin-α-tocopherol nano-micelles in seizing tacrolimus renal toxicity, managing rheumatoid arthritis and accelerating bone regeneration |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/6a9ece2bbec441c1a0e6289921903cb6 |
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oai:doaj.org-article:6a9ece2bbec441c1a0e6289921903cb62021-12-02T16:51:10ZPotential Privilege of Maltodextrin-α-Tocopherol Nano-Micelles in Seizing Tacrolimus Renal Toxicity, Managing Rheumatoid Arthritis and Accelerating Bone Regeneration1178-2013https://doaj.org/article/6a9ece2bbec441c1a0e6289921903cb62021-07-01T00:00:00Zhttps://www.dovepress.com/potential-privilege-of-maltodextrin--tocopherol-nano-micelles-in-seizi-peer-reviewed-fulltext-article-IJNhttps://doaj.org/toc/1178-2013Hala M Helal,1 Wael M Samy,1 Elbadawy A Kamoun,2,3 Esmail M El-Fakharany,4 Doaa A Abdelmonsif,5,6 Rania G Aly,7 Sana M Mortada,1 Marwa A Sallam1 1Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt; 2Polymeric Materials Research Dep., Advanced Technology and New Materials Research Institute (ATNMRI), City of Scientific Research and Technological Applications (SRTA-City), New Borg Al-Arab City, Alexandria, 21934, Egypt; 3Nanotechnology Research Center (NTRC), The British University in Egypt (BUE), El- Sherouk City, Cairo, 11837, Egypt; 4Proteins Research Dep., Genetic Engineering and Biotechnology Research Institute (GEBRI), City of Scientific Research and Technological Applications (SRTA-City), New Borg Al-Arab City, Alexandria, 21934, Egypt; 5Department of Medical Biochemistry, Faculty of Medicine, Alexandria University, Alexandria, 21521, Egypt; 6Center of Excellence for Research in Regenerative Medicine and Applications (CERRMA), Faculty of Medicine, Alexandria University, Alexandria, 21521, Egypt; 7Department of Surgical Pathology, Faculty of Medicine, Alexandria University, Alexandria, 21521, EgyptCorrespondence: Marwa A SallamDepartment of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, EgyptTel +20 3 4868256Fax +20 3 4871668Email marwa.sallam@alexu.edu.egElbadawy A KamounPolymeric Materials Research Dep., Advanced Technology and New Materials Research Institute (ATNMRI), City of Scientific Research and Technological Applications (SRTA-City), New Borg Al-Arab City, Alexandria, 21934, EgyptTel +20 1283320302Email e-b.kamoun@tu-bs.deBackground: 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.Keywords: polymeric micelles, vitamin E, osteopontin, SOX9, rheumatoidHelal HMSamy WMKamoun EAEl-Fakharany EMAbdelmonsif DAAly RGMortada SMSallam MADove Medical Pressarticlepolymeric micellesvitamin eosteopontinsox9rheumatoidMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 4781-4803 (2021) |