Nanoparticles of cisplatin augment drug accumulations and inhibit multidrug resistance transporters in human glioblastoma cells
Background: Cisplatin (CSP) is a potent anticancer drug widely used in treating glioblastoma multiforme (GBM). However, CSP's clinical efficacy in GBM contrasted with low therapeutic ratio, toxicity, and multidrug resistance (MDR). Therefore, we have developed a system for the active targeting...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-08-01
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| Series: | Saudi Pharmaceutical Journal |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1319016421001286 |
| _version_ | 1818915979519852544 |
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| author | Naseer Maliyakkal Asmy Appadath Beeran Nayanabhirama Udupa |
| author_facet | Naseer Maliyakkal Asmy Appadath Beeran Nayanabhirama Udupa |
| author_sort | Naseer Maliyakkal |
| collection | DOAJ |
| description | Background: Cisplatin (CSP) is a potent anticancer drug widely used in treating glioblastoma multiforme (GBM). However, CSP's clinical efficacy in GBM contrasted with low therapeutic ratio, toxicity, and multidrug resistance (MDR). Therefore, we have developed a system for the active targeting of cisplatin in GBM via cisplatin loaded polymeric nanoplatforms (CSP-NPs). Methods: CSP-NPs were prepared by modified double emulsion and nanoprecipitation techniques. The physiochemical characterizations of CSP-NPs were performed using zeta sizer, scanning electron microscopy (SEM), drug release kinetics, and drug content analysis. Cytotoxicity, induction of apoptosis, and cell cycle-specific activity of CSP-NPs in human GBM cell lines were evaluated by MTT assay, fluorescent microscopy, and flow cytometry. Intracellular drug uptake was gauged by fluorescent imaging and flow cytometry. The potential of CSP-NPs to inhibit MDR transporters were assessed by flow cytometry-based drug efflux assays. Results: CSP-NPs have smooth surface properties with discrete particle size with required zeta potential, polydispersity index, drug entrapment efficiency, and drug content. CSP-NPs has demonstrated an ‘initial burst effect’ followed by sustained drug release properties. CSP-NPs imparted dose and time-dependent cytotoxicity and triggered apoptosis in human GBM cells. Interestingly, CSP-NPs significantly increased uptake, internalization, and accumulations of anticancer drugs. Moreover, CSP-NPs significantly reversed the MDR transporters (ABCB1 and ABCG2) in human GBM cells. Conclusion: The nanoparticulate system of cisplatin seems to has a promising potential for active targeting of cisplatin as an effective and specific therapeutic for human GBM, thus eliminating current chemotherapy's limitations. |
| first_indexed | 2024-12-20T00:10:53Z |
| format | Article |
| id | doaj.art-7806c3aea30f493998dc6b7b2d59c3e7 |
| institution | Directory Open Access Journal |
| issn | 1319-0164 |
| language | English |
| last_indexed | 2024-12-20T00:10:53Z |
| publishDate | 2021-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Saudi Pharmaceutical Journal |
| spelling | doaj.art-7806c3aea30f493998dc6b7b2d59c3e72022-12-21T20:00:30ZengElsevierSaudi Pharmaceutical Journal1319-01642021-08-01298857873Nanoparticles of cisplatin augment drug accumulations and inhibit multidrug resistance transporters in human glioblastoma cellsNaseer Maliyakkal0Asmy Appadath Beeran1Nayanabhirama Udupa2Department of Basic Medical Sciences, College of Applied Medical Sciences in Khamis Mushait, King Khalid University, Abha, Saudi Arabia; Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India; Cancer Research Unit, King Khalid University, Abha, Saudi Arabia; Corresponding author at: Dr. Naseer Maliyakkal, Assistant Professor, Department of Basic Medical Sciences, College of Applied Medical Sciences in Khamis Mushait, King Khalid University, Abha, Saudi Arabia.Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, IndiaManipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, IndiaBackground: Cisplatin (CSP) is a potent anticancer drug widely used in treating glioblastoma multiforme (GBM). However, CSP's clinical efficacy in GBM contrasted with low therapeutic ratio, toxicity, and multidrug resistance (MDR). Therefore, we have developed a system for the active targeting of cisplatin in GBM via cisplatin loaded polymeric nanoplatforms (CSP-NPs). Methods: CSP-NPs were prepared by modified double emulsion and nanoprecipitation techniques. The physiochemical characterizations of CSP-NPs were performed using zeta sizer, scanning electron microscopy (SEM), drug release kinetics, and drug content analysis. Cytotoxicity, induction of apoptosis, and cell cycle-specific activity of CSP-NPs in human GBM cell lines were evaluated by MTT assay, fluorescent microscopy, and flow cytometry. Intracellular drug uptake was gauged by fluorescent imaging and flow cytometry. The potential of CSP-NPs to inhibit MDR transporters were assessed by flow cytometry-based drug efflux assays. Results: CSP-NPs have smooth surface properties with discrete particle size with required zeta potential, polydispersity index, drug entrapment efficiency, and drug content. CSP-NPs has demonstrated an ‘initial burst effect’ followed by sustained drug release properties. CSP-NPs imparted dose and time-dependent cytotoxicity and triggered apoptosis in human GBM cells. Interestingly, CSP-NPs significantly increased uptake, internalization, and accumulations of anticancer drugs. Moreover, CSP-NPs significantly reversed the MDR transporters (ABCB1 and ABCG2) in human GBM cells. Conclusion: The nanoparticulate system of cisplatin seems to has a promising potential for active targeting of cisplatin as an effective and specific therapeutic for human GBM, thus eliminating current chemotherapy's limitations.http://www.sciencedirect.com/science/article/pii/S1319016421001286Cisplatin nanoparticlesActive drug targetingTargeting multidrug resistance (MDR) transportersInduction of ApoptosisDrug uptake and accumulations |
| spellingShingle | Naseer Maliyakkal Asmy Appadath Beeran Nayanabhirama Udupa Nanoparticles of cisplatin augment drug accumulations and inhibit multidrug resistance transporters in human glioblastoma cells Saudi Pharmaceutical Journal Cisplatin nanoparticles Active drug targeting Targeting multidrug resistance (MDR) transporters Induction of Apoptosis Drug uptake and accumulations |
| title | Nanoparticles of cisplatin augment drug accumulations and inhibit multidrug resistance transporters in human glioblastoma cells |
| title_full | Nanoparticles of cisplatin augment drug accumulations and inhibit multidrug resistance transporters in human glioblastoma cells |
| title_fullStr | Nanoparticles of cisplatin augment drug accumulations and inhibit multidrug resistance transporters in human glioblastoma cells |
| title_full_unstemmed | Nanoparticles of cisplatin augment drug accumulations and inhibit multidrug resistance transporters in human glioblastoma cells |
| title_short | Nanoparticles of cisplatin augment drug accumulations and inhibit multidrug resistance transporters in human glioblastoma cells |
| title_sort | nanoparticles of cisplatin augment drug accumulations and inhibit multidrug resistance transporters in human glioblastoma cells |
| topic | Cisplatin nanoparticles Active drug targeting Targeting multidrug resistance (MDR) transporters Induction of Apoptosis Drug uptake and accumulations |
| url | http://www.sciencedirect.com/science/article/pii/S1319016421001286 |
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