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Harnessing Folate-Functionalized Nasal Delivery of Dox–Erlo-Loaded Biopolymeric Nanoparticles in Cancer Treatment: Development, Optimization, Characterization, and Biodistribution Analysis
The aim of the present study is to develop Doxorubicin–Erlotinib nanoparticles (Dox–Erlo NPs) and folate-armored Dox–Erlo-NP conjugates for targeting glioma cancer. Glioma is one of the most common progressive cancerous growths originating from brain glial cells. However, the blood–brain barrier (BB...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9959140/ https://www.ncbi.nlm.nih.gov/pubmed/37259356 http://dx.doi.org/10.3390/ph16020207 |
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author | Farheen, Ms Akhter, Md Habban Chitme, Havagiray Akhter, Md Sayeed Tabassum, Fauzia Jaremko, Mariusz Emwas, Abdul-Hamid |
author_facet | Farheen, Ms Akhter, Md Habban Chitme, Havagiray Akhter, Md Sayeed Tabassum, Fauzia Jaremko, Mariusz Emwas, Abdul-Hamid |
author_sort | Farheen, Ms |
collection | PubMed |
description | The aim of the present study is to develop Doxorubicin–Erlotinib nanoparticles (Dox–Erlo NPs) and folate-armored Dox–Erlo-NP conjugates for targeting glioma cancer. Glioma is one of the most common progressive cancerous growths originating from brain glial cells. However, the blood–brain barrier (BBB) is only semi-permeable and is highly selective as to which compounds are let through; designing compounds that overcome this constraint is therefore a major challenge in the development of pharmaceutical agents. We demonstrate that the NP conjugates studied in this paper may ameliorate the BBB penetration and enrich the drug concentration in the target bypassing the BBB. NPs were prepared using a biopolymer with a double-emulsion solvent evaporation technique and functionalized with folic acid for site-specific targeting. Dox–Erlo NPs and Dox–Erlo-NP conjugates were extensively characterized in vitro for various parameters. Dox–Erlo NPs and Dox–Erlo-NP conjugates incurred a z-average of 95.35 ± 10.25 nm and 110.12 ± 9.2 nm, respectively. The zeta potentials of the Dox–Erlo NPs and Dox–Erlo-NP conjugates were observed at −18.1 mV and −25.1 mV, respectively. A TEM image has shown that the NPs were well-dispersed, uniform, de-aggregated, and consistent. A hemolytic assay confirmed hemocompatibility with the developed formulation and that it can be safely administered. Dox–Erlo-NP conjugates significantly reduced the number of viable cells to 24.66 ± 2.08% and 32.33 ± 2.51% in U87 and C6 cells, respectively, and IC50 values of 3.064 µM and 3.350 µM in U87 and C6 cells were reported after 24 h, respectively. A biodistribution study revealed that a significant concentration of Dox and Erlo were estimated in the brain relative to drug suspension. Dox–Erlo-NP conjugates were also stable for three months. The findings suggest that the developed Dox–Erlo-NP conjugates may be a promising agent for administration in glioma therapy. |
format | Online Article Text |
id | pubmed-9959140 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99591402023-02-26 Harnessing Folate-Functionalized Nasal Delivery of Dox–Erlo-Loaded Biopolymeric Nanoparticles in Cancer Treatment: Development, Optimization, Characterization, and Biodistribution Analysis Farheen, Ms Akhter, Md Habban Chitme, Havagiray Akhter, Md Sayeed Tabassum, Fauzia Jaremko, Mariusz Emwas, Abdul-Hamid Pharmaceuticals (Basel) Article The aim of the present study is to develop Doxorubicin–Erlotinib nanoparticles (Dox–Erlo NPs) and folate-armored Dox–Erlo-NP conjugates for targeting glioma cancer. Glioma is one of the most common progressive cancerous growths originating from brain glial cells. However, the blood–brain barrier (BBB) is only semi-permeable and is highly selective as to which compounds are let through; designing compounds that overcome this constraint is therefore a major challenge in the development of pharmaceutical agents. We demonstrate that the NP conjugates studied in this paper may ameliorate the BBB penetration and enrich the drug concentration in the target bypassing the BBB. NPs were prepared using a biopolymer with a double-emulsion solvent evaporation technique and functionalized with folic acid for site-specific targeting. Dox–Erlo NPs and Dox–Erlo-NP conjugates were extensively characterized in vitro for various parameters. Dox–Erlo NPs and Dox–Erlo-NP conjugates incurred a z-average of 95.35 ± 10.25 nm and 110.12 ± 9.2 nm, respectively. The zeta potentials of the Dox–Erlo NPs and Dox–Erlo-NP conjugates were observed at −18.1 mV and −25.1 mV, respectively. A TEM image has shown that the NPs were well-dispersed, uniform, de-aggregated, and consistent. A hemolytic assay confirmed hemocompatibility with the developed formulation and that it can be safely administered. Dox–Erlo-NP conjugates significantly reduced the number of viable cells to 24.66 ± 2.08% and 32.33 ± 2.51% in U87 and C6 cells, respectively, and IC50 values of 3.064 µM and 3.350 µM in U87 and C6 cells were reported after 24 h, respectively. A biodistribution study revealed that a significant concentration of Dox and Erlo were estimated in the brain relative to drug suspension. Dox–Erlo-NP conjugates were also stable for three months. The findings suggest that the developed Dox–Erlo-NP conjugates may be a promising agent for administration in glioma therapy. MDPI 2023-01-30 /pmc/articles/PMC9959140/ /pubmed/37259356 http://dx.doi.org/10.3390/ph16020207 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Farheen, Ms Akhter, Md Habban Chitme, Havagiray Akhter, Md Sayeed Tabassum, Fauzia Jaremko, Mariusz Emwas, Abdul-Hamid Harnessing Folate-Functionalized Nasal Delivery of Dox–Erlo-Loaded Biopolymeric Nanoparticles in Cancer Treatment: Development, Optimization, Characterization, and Biodistribution Analysis |
title | Harnessing Folate-Functionalized Nasal Delivery of Dox–Erlo-Loaded Biopolymeric Nanoparticles in Cancer Treatment: Development, Optimization, Characterization, and Biodistribution Analysis |
title_full | Harnessing Folate-Functionalized Nasal Delivery of Dox–Erlo-Loaded Biopolymeric Nanoparticles in Cancer Treatment: Development, Optimization, Characterization, and Biodistribution Analysis |
title_fullStr | Harnessing Folate-Functionalized Nasal Delivery of Dox–Erlo-Loaded Biopolymeric Nanoparticles in Cancer Treatment: Development, Optimization, Characterization, and Biodistribution Analysis |
title_full_unstemmed | Harnessing Folate-Functionalized Nasal Delivery of Dox–Erlo-Loaded Biopolymeric Nanoparticles in Cancer Treatment: Development, Optimization, Characterization, and Biodistribution Analysis |
title_short | Harnessing Folate-Functionalized Nasal Delivery of Dox–Erlo-Loaded Biopolymeric Nanoparticles in Cancer Treatment: Development, Optimization, Characterization, and Biodistribution Analysis |
title_sort | harnessing folate-functionalized nasal delivery of dox–erlo-loaded biopolymeric nanoparticles in cancer treatment: development, optimization, characterization, and biodistribution analysis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9959140/ https://www.ncbi.nlm.nih.gov/pubmed/37259356 http://dx.doi.org/10.3390/ph16020207 |
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