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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Autores principales:	Salim SA, Kamoun EA, Evans S, EL-Moslamy SH, El-Fakharany EM, Elmazar MM, Abdel-Aziz AF, Abou-Saleh RH, Salaheldin TA
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	sandwich scaffold pcl/pmma 6-mp sustained drug release anticancer Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/e5f839e68c3541d7bbfc0ac3cb83fa9e
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id	oai:doaj.org-article:e5f839e68c3541d7bbfc0ac3cb83fa9e
record_format	dspace
institution	DOAJ
collection	DOAJ
language	EN
topic	sandwich scaffold pcl/pmma 6-mp sustained drug release anticancer Medicine (General) R5-920
spellingShingle	sandwich scaffold pcl/pmma 6-mp sustained drug release anticancer Medicine (General) R5-920 Salim SA Kamoun EA Evans S EL-Moslamy SH El-Fakharany EM Elmazar MM Abdel-Aziz AF Abou-Saleh RH Salaheldin TA 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
description	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
format	article
author	Salim SA Kamoun EA Evans S EL-Moslamy SH El-Fakharany EM Elmazar MM Abdel-Aziz AF Abou-Saleh RH Salaheldin TA
author_facet	Salim SA Kamoun EA Evans S EL-Moslamy SH El-Fakharany EM Elmazar MM Abdel-Aziz AF Abou-Saleh RH Salaheldin TA
author_sort	Salim SA
title	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
title_short	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
title_full	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
title_fullStr	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
title_full_unstemmed	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
title_sort	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
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/e5f839e68c3541d7bbfc0ac3cb83fa9e
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spelling	oai:doaj.org-article:e5f839e68c3541d7bbfc0ac3cb83fa9e2021-12-02T18:39:02ZMercaptopurine-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 Tests1178-2013https://doaj.org/article/e5f839e68c3541d7bbfc0ac3cb83fa9e2021-10-01T00:00:00Zhttps://www.dovepress.com/mercaptopurine-loaded-sandwiched-tri-layered-composed-of-electrospun-p-peer-reviewed-fulltext-article-IJNhttps://doaj.org/toc/1178-2013Samar 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 methacrylateSalim SAKamoun EAEvans SEL-Moslamy SHEl-Fakharany EMElmazar MMAbdel-Aziz AFAbou-Saleh RHSalaheldin TADove Medical Pressarticlesandwich scaffoldpcl/pmma6-mpsustained drug releaseanticancerMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 6937-6955 (2021)

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

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