Mercaptopurine-Loaded Sandwiched Tri-Layered Composed of Electrospun Polycaprolactone/Poly(Methyl Methacrylate) Nanofibrous Scaffolds as Anticancer Carrier with Antimicrobial and Antibiotic Features: Sandwich Configuration Nanofibers, Release Study and in vitro Bioevaluation Tests
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, C...
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| Formato: | article |
| Lenguaje: | EN |
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Dove Medical Press
2021
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| Acceso en línea: | https://doaj.org/article/e5f839e68c3541d7bbfc0ac3cb83fa9e |
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| Sumario: | 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 |
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