Search

Samar A Salim,1,2 Elbadawy A Kamoun,1,3 Stephen Evans,4 Shahira H EL-Moslamy,5 Esmail M El-Fakharany,6 Mohamed M Elmazar,7 AF Abdel-Aziz,2 RH Abou-Saleh,8,9 Taher A Salaheldin10 1Nanotechnology Research Center (NTRC), The British University in Egypt (BUE), Cairo, 11837, Egypt; 2Biochemistry Group, Chemistry Dep., Faculty of Science, Mansoura University, Mansoura, Egypt; 3Polymeric Materials Research Dep., Advanced Technology and New Materials Research Institute (ATNMRI), City of Scientific Research and Technological Applications (SRTA-City), Alexandria, 21934, Egypt; 4Molecular and Nanoscale Physics Group, School of Physics and Astronomy, University of Leeds, Leeds, LS2 9JT, UK; 5Bioprocess Development Dep., GEBRI, City of Scientific Research and Technological Applications (SRTA-City), Alexandria, 21934, Egypt; 6Protein Research Dep. GEBRI, City of Scientific Research and Technological Applications (SRTA-City), Alexandria, 21934, Egypt; 7Faculty of Pharmacy, The British University in Egypt (BUE), Cairo, 11837, Egypt; 8Biophysics Group, Dep. of Physics, Faculty of Science, Mansoura University, Mansoura, Egypt; 9Nanoscience and Technology Program, Faculty of Advanced Basic Science, Galala University, Suez, Egypt; 10Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY, 12144, USACorrespondence: Elbadawy A Kamoun Email e-b.kamoun@tu-bs.de; badawykamoun@yahoo.comBackground: 6-Mercaptopurine (6-MP) is a potential anti-cancer agent which its therapeutic and limitation applicability due to its high toxicity.Objective: Herein, 6-MP was loaded into tri-layered sandwich nanofibrous scaffold (the top layer composed of poly methyl methacrylate/polycaprolactone (PMMA/PCL), the middle layer was PCL/PMMA/6-MP, and the bottom layer was PCL/PMMA to improve its bioactivity, adjusting the release-sustainability and reduce its toxicity.Methods: Electrospun tri-layered nanofibers composed of PCL/PMMA were utilized as nano-mats for controlling sustained drug release. Four groups of sandwich scaffold configurations were investigated with alteration of (PMMA: PCL) composition.Results: The sandwich scaffold composed of 2%PCL/4%PMMA/1%6-MP showed the best miscibility, good homogeneity and produced the smoothest nanofibers and low crystallinity. All fabricated 6-MP-loaded-PCL/PMMA scaffolds exhibited antimicrobial properties on the bacterial and fungal organisms, where the cytotoxicity evaluation proved the safety of scaffolds on normal cells, even at high concentration. Scaffolds provided a sustained-drug release profile that was strongly dependent on (PCL: PMMA). As (PCL: PMMA) decreased, the sustained 6-MP release from PCL/PMMA scaffolds increased. Results established that ∼ 18% and 20% of 6-MP were released after 23h from (4%PCL/4%PMMA/1%6-MP) and (2%PCL/4%PMMA/1%6-MP), respectively, where this release was maintained for more than 20 days. The anti-cancer activity of all fabricated scaffolds was also investigated using different cancerous cell lines (e.g., Caco-2, MDA, and HepG-2) results showed that 6-MP-loaded-nanofibrous mats have an anti-cancer effect, with a high selective index for breast cancer. We observed that viability of a cancer cell was dropped to about 10%, using nanofibers containing 2%PCL/4%PMMA/1%6-MP.Conclusion: Overall, the PCL: PMMA ratio and sandwich configuration imparts a tight control on long-term release profile and initial burst of 6-MP for anticancer treatment purposes.Keywords: sandwich scaffold, PCL/PMMA, 6-MP, sustained drug release, anticancer, 6-Mercaptopurine, polycaprolactone/poly methyl methacrylate

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

Sarah A El-Lakany,1 Ahmed I Abd-Elhamid,2 Elbadawy A Kamoun,3,4 Esmail M El-Fakharany,5 Wael M Samy,1 Nazik A Elgindy1 1Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; 2Nanotechnology and Composite Material Research Department, Advanced Technology and New Materials Research Institute, City of Scientific Research and Technological Applications (SRTA-City), Alexandria 21934, Egypt; 3Polymeric Materials Research Department, Advanced Technology and New Materials Research Institute, City of Scientific Research and Technological Applications (SRTA-City), Alexandria 21934, Egypt; 4Nanotechnology Research Center (NTRC), The British University in Egypt (BUE), El-Sherouk City, Cairo 11837, Egypt; 5Therapeutic and Protective Proteins Laboratory, Protein Research Department, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technological Applications (SRTA-City), Alexandria 21934, EgyptCorrespondence: Sarah A El-LakanyDepartment of Industrial Pharmacy Faculty of Pharmacy, Alexandria University, 1 El Khartoum Square, PO Box 21521, Alexandria, EgyptTel +20 3 1002828663Fax +20 3 4871668Email sarah.ellakany@alexu.edu.egObjectives: Novel α-bisabolol (BIS)-loaded citric acid cross-linked zein nanofibrous scaffolds (C-ZNFs) were proposed to serve as safe platforms for promoting wound repair in rats.Methods: ZNFs were synthesized using electrospinning technique, then NFs, with adequate water resistance, were produced using citric acid as a safe cross-linker.Results: Compared to the uncross-linked ZNFs, cross-linking with 7% w/w citric acid decreased swelling index by 3 folds, while the tensile strength and the contact angle were enhanced to 2.5 and 3.8 folds, respectively. SEM images showed beads-free homogeneous NFs with a fully inter-connected 3D-network, where the average diameter of optimized C-ZNFs was 181.7±50 nm. After 24 h, C-ZNFs exhibited a decreased BIS release rate (45.6%), compared to uncross-linked mats (84.9%). By increasing BIS concentration, the cell adhesion (WI38 fibroblasts) was improved which can be attributed mainly to BIS activation of transforming growth factor-beta (TGF-β1). The MTT-OD obtained values indicated that all tested zein scaffolds significantly enhanced the viability of WI38 fibroblasts, compared to the control after 48h of incubation which can be referred to the proliferative potential of zein by provoking cell spreading process. The scratch wound assay demonstrated that BIS-loaded ZNF scaffolds showed accelerated migration and proliferation of fibroblasts expressed by significantly higher wound closure rates compared to the control sample. BIS-loaded-C-ZNFs prominently accelerated tissue regeneration for wound closure demonstrated by entirely grown epithelium with normal keratinization and rapid wound contraction, compared to the control. Immunohistochemical results confirmed the superiority of BIS-loaded-C-ZNFs, where the observed reduced NF-κB and the elevated cytokeratin expressions confirmed the anti-inflammatory and proliferative effects of the scaffolds, respectively.Conclusion: In-vitro, optimized C-ZNFs offered a satisfactory cytocompatibility, adhesion and healing which were consistent with the in-vivo results. BIS-loaded-C-ZNFs could be regarded as a promising and effective biomaterial for tissue regeneration and for accelerating the wound healing process.Keywords: cell compatibility, electrospinning, German chamomile, fiber mats