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Surface-Modified Biobased Polymeric Nanoparticles for Dual Delivery of Doxorubicin and Gefitinib in Glioma Cell Lines

[Image: see text] Glioma is a malignant form of brain cancer that is challenging to treat due to the progressive growth of glial cells. To target overexpressed folate receptors in glioma brain tumors, we designed and investigated doxorubicin–gefitinib nanoparticles (Dox-Gefit NPs) and folate conjuga...

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Autores principales: Farheen, Ms, Akhter, Md Habban, Chitme, Havagiray, Suliman, Muath, Jaremko, Mariusz, Emwas, Abdul-Hamid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10413376/
https://www.ncbi.nlm.nih.gov/pubmed/37576633
http://dx.doi.org/10.1021/acsomega.3c01375
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author Farheen, Ms
Akhter, Md Habban
Chitme, Havagiray
Suliman, Muath
Jaremko, Mariusz
Emwas, Abdul-Hamid
author_facet Farheen, Ms
Akhter, Md Habban
Chitme, Havagiray
Suliman, Muath
Jaremko, Mariusz
Emwas, Abdul-Hamid
author_sort Farheen, Ms
collection PubMed
description [Image: see text] Glioma is a malignant form of brain cancer that is challenging to treat due to the progressive growth of glial cells. To target overexpressed folate receptors in glioma brain tumors, we designed and investigated doxorubicin–gefitinib nanoparticles (Dox-Gefit NPs) and folate conjugated Dox-Gefit NPs (Dox-Gefit NPs-F). Dox-Gefit NPs and Dox-Gefit NPs-F were characterized by multiple techniques including Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), proton nuclear magnetic resonance ((1)H NMR), and transmission electron microscopy (TEM). In vitro release profiles were measured at both physiological and tumor endosomal pH. The cytotoxicity of the Dox-Gefit NP formulations was measured against C6 and U87 glioma cell lines. A hemolysis assay was performed to investigate biocompatibility of the formulations, and distribution of the drugs in different organs was also estimated. The Dox-Gefit NPs and Dox-Gefit NPs-F were 109.45 ± 7.26 and 120.35 ± 3.65 nm in size and had surface charges of −18.0 ± 3.27 and −20.0 ± 8.23 mV, respectively. Dox-Gefit NPs and Dox-Gefit NPs-F significantly reduced the growth of U87 cells, with IC(50) values of 9.9 and 3.2 μM. Similarly, growth of the C6 cell line was significantly reduced, with IC(50) values of 8.43 and 3.31 μM after a 24 h incubation, in Dox-Gefit NPs and Dox-Gefit NPs-F, respectively. The percentage drug releases of Dox and Gefit from Dox-Gefit NPs at pH 7.4 were 60.87 ± 0.59 and 68.23 ± 0.1%, respectively. Similarly, at pH 5.4, Dox and Gefit releases from NPs were 70.87 ± 0.28 and 69.24 ± 0.12%, respectively. Biodistribution analysis revealed that more Dox and Gefit were present in the brain than in the other organs. The functionalized NPs inhibited the growth of glioma cells due to high drug concentrations in the brain. Folate conjugated NPs of Dox-Gefit could be a treatment option in glioma therapy.
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spelling pubmed-104133762023-08-11 Surface-Modified Biobased Polymeric Nanoparticles for Dual Delivery of Doxorubicin and Gefitinib in Glioma Cell Lines Farheen, Ms Akhter, Md Habban Chitme, Havagiray Suliman, Muath Jaremko, Mariusz Emwas, Abdul-Hamid ACS Omega [Image: see text] Glioma is a malignant form of brain cancer that is challenging to treat due to the progressive growth of glial cells. To target overexpressed folate receptors in glioma brain tumors, we designed and investigated doxorubicin–gefitinib nanoparticles (Dox-Gefit NPs) and folate conjugated Dox-Gefit NPs (Dox-Gefit NPs-F). Dox-Gefit NPs and Dox-Gefit NPs-F were characterized by multiple techniques including Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), proton nuclear magnetic resonance ((1)H NMR), and transmission electron microscopy (TEM). In vitro release profiles were measured at both physiological and tumor endosomal pH. The cytotoxicity of the Dox-Gefit NP formulations was measured against C6 and U87 glioma cell lines. A hemolysis assay was performed to investigate biocompatibility of the formulations, and distribution of the drugs in different organs was also estimated. The Dox-Gefit NPs and Dox-Gefit NPs-F were 109.45 ± 7.26 and 120.35 ± 3.65 nm in size and had surface charges of −18.0 ± 3.27 and −20.0 ± 8.23 mV, respectively. Dox-Gefit NPs and Dox-Gefit NPs-F significantly reduced the growth of U87 cells, with IC(50) values of 9.9 and 3.2 μM. Similarly, growth of the C6 cell line was significantly reduced, with IC(50) values of 8.43 and 3.31 μM after a 24 h incubation, in Dox-Gefit NPs and Dox-Gefit NPs-F, respectively. The percentage drug releases of Dox and Gefit from Dox-Gefit NPs at pH 7.4 were 60.87 ± 0.59 and 68.23 ± 0.1%, respectively. Similarly, at pH 5.4, Dox and Gefit releases from NPs were 70.87 ± 0.28 and 69.24 ± 0.12%, respectively. Biodistribution analysis revealed that more Dox and Gefit were present in the brain than in the other organs. The functionalized NPs inhibited the growth of glioma cells due to high drug concentrations in the brain. Folate conjugated NPs of Dox-Gefit could be a treatment option in glioma therapy. American Chemical Society 2023-07-26 /pmc/articles/PMC10413376/ /pubmed/37576633 http://dx.doi.org/10.1021/acsomega.3c01375 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Farheen, Ms
Akhter, Md Habban
Chitme, Havagiray
Suliman, Muath
Jaremko, Mariusz
Emwas, Abdul-Hamid
Surface-Modified Biobased Polymeric Nanoparticles for Dual Delivery of Doxorubicin and Gefitinib in Glioma Cell Lines
title Surface-Modified Biobased Polymeric Nanoparticles for Dual Delivery of Doxorubicin and Gefitinib in Glioma Cell Lines
title_full Surface-Modified Biobased Polymeric Nanoparticles for Dual Delivery of Doxorubicin and Gefitinib in Glioma Cell Lines
title_fullStr Surface-Modified Biobased Polymeric Nanoparticles for Dual Delivery of Doxorubicin and Gefitinib in Glioma Cell Lines
title_full_unstemmed Surface-Modified Biobased Polymeric Nanoparticles for Dual Delivery of Doxorubicin and Gefitinib in Glioma Cell Lines
title_short Surface-Modified Biobased Polymeric Nanoparticles for Dual Delivery of Doxorubicin and Gefitinib in Glioma Cell Lines
title_sort surface-modified biobased polymeric nanoparticles for dual delivery of doxorubicin and gefitinib in glioma cell lines
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10413376/
https://www.ncbi.nlm.nih.gov/pubmed/37576633
http://dx.doi.org/10.1021/acsomega.3c01375
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