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Development, Optimization and Evaluation of 2-Methoxy-Estradiol Loaded Nanocarrier for Prostate Cancer
The therapeutic efficacy of antineoplastic agents possessing a selective target to the nucleus of the cancer cells could be enhanced through novel formulation approaches. Thus, toward the improvement of the anticancer potential of 2-methoxy estradiol (2 ME) on prostate cancer, the drug was entrapped...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322574/ https://www.ncbi.nlm.nih.gov/pubmed/34335251 http://dx.doi.org/10.3389/fphar.2021.682337 |
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author | Alhakamy, Nabil A. Ahmed, Osama A. Fahmy, Usama A. Asfour, Hani Z. Alghaith, Adel F. Mahdi, Wael A. Alshehri, Sultan Md, Shadab |
author_facet | Alhakamy, Nabil A. Ahmed, Osama A. Fahmy, Usama A. Asfour, Hani Z. Alghaith, Adel F. Mahdi, Wael A. Alshehri, Sultan Md, Shadab |
author_sort | Alhakamy, Nabil A. |
collection | PubMed |
description | The therapeutic efficacy of antineoplastic agents possessing a selective target to the nucleus of the cancer cells could be enhanced through novel formulation approaches. Thus, toward the improvement of the anticancer potential of 2-methoxy estradiol (2 ME) on prostate cancer, the drug was entrapped into the hydrophobic micelles core formulated with Phospholipon 90G and d-α-tocopheryl polyethylene glycol succinate (TPGS). Optimization of the formulation was done by Box-Behnken statistical design using Statgraphics software to standardize percentages of TPGS and phospholipid to obtain the smallest particle size. The optimized formulation was found to be spherical with nanometer size of 152 ± 5.2 nm, and low PDI (0.234). The entrapment efficiency of the micelles was 88.67 ± 3.21% with >93% release of 2 ME within 24 h. There was a 16-fold increase in apoptosis and an 8-fold increase in necrosis of the PC-3 cells when incubated with 2 ME micellar delivery compared to control cells (2.8 ± 0.2%). This increased apoptosis was further correlated with increased BAX expression (11.6 ± 0.7) and decreased BCL-2 expression (0.29 ± 0.05) in 2 ME micelles treated cells when compared to the control group. Further, loss of mitochondrial membrane potential (∼50-fold) by the drug-loaded micelles and free drug compared to control cells was found to be due to the generation of ROS. Findings on cell cycle analysis revealed the significant arrest of the G2-M phase of the PC-3 cells when incubated with the optimized formulation. Simultaneously, a significantly increased number of cells in pre-G1 revealed the maximum apoptotic potential of the drug when delivered via micellar formulation. Finally, upregulation of caspase-9, p53, and NO, with downregulation of TNF-α, NF-κβ, and inflammatory mediators of the PC-3 cells established the superiority of the micellar approach against prostate cancer. In summary, the acquired results highlighted the potentiality of the 2 ME-micellar delivery tool for controlling the growth of prostate cancer cells for improved efficacy. |
format | Online Article Text |
id | pubmed-8322574 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83225742021-07-31 Development, Optimization and Evaluation of 2-Methoxy-Estradiol Loaded Nanocarrier for Prostate Cancer Alhakamy, Nabil A. Ahmed, Osama A. Fahmy, Usama A. Asfour, Hani Z. Alghaith, Adel F. Mahdi, Wael A. Alshehri, Sultan Md, Shadab Front Pharmacol Pharmacology The therapeutic efficacy of antineoplastic agents possessing a selective target to the nucleus of the cancer cells could be enhanced through novel formulation approaches. Thus, toward the improvement of the anticancer potential of 2-methoxy estradiol (2 ME) on prostate cancer, the drug was entrapped into the hydrophobic micelles core formulated with Phospholipon 90G and d-α-tocopheryl polyethylene glycol succinate (TPGS). Optimization of the formulation was done by Box-Behnken statistical design using Statgraphics software to standardize percentages of TPGS and phospholipid to obtain the smallest particle size. The optimized formulation was found to be spherical with nanometer size of 152 ± 5.2 nm, and low PDI (0.234). The entrapment efficiency of the micelles was 88.67 ± 3.21% with >93% release of 2 ME within 24 h. There was a 16-fold increase in apoptosis and an 8-fold increase in necrosis of the PC-3 cells when incubated with 2 ME micellar delivery compared to control cells (2.8 ± 0.2%). This increased apoptosis was further correlated with increased BAX expression (11.6 ± 0.7) and decreased BCL-2 expression (0.29 ± 0.05) in 2 ME micelles treated cells when compared to the control group. Further, loss of mitochondrial membrane potential (∼50-fold) by the drug-loaded micelles and free drug compared to control cells was found to be due to the generation of ROS. Findings on cell cycle analysis revealed the significant arrest of the G2-M phase of the PC-3 cells when incubated with the optimized formulation. Simultaneously, a significantly increased number of cells in pre-G1 revealed the maximum apoptotic potential of the drug when delivered via micellar formulation. Finally, upregulation of caspase-9, p53, and NO, with downregulation of TNF-α, NF-κβ, and inflammatory mediators of the PC-3 cells established the superiority of the micellar approach against prostate cancer. In summary, the acquired results highlighted the potentiality of the 2 ME-micellar delivery tool for controlling the growth of prostate cancer cells for improved efficacy. Frontiers Media S.A. 2021-07-16 /pmc/articles/PMC8322574/ /pubmed/34335251 http://dx.doi.org/10.3389/fphar.2021.682337 Text en Copyright © 2021 Alhakamy, Ahmed, Fahmy, Asfour, Alghaith, Mahdi, Alshehri and Md. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Alhakamy, Nabil A. Ahmed, Osama A. Fahmy, Usama A. Asfour, Hani Z. Alghaith, Adel F. Mahdi, Wael A. Alshehri, Sultan Md, Shadab Development, Optimization and Evaluation of 2-Methoxy-Estradiol Loaded Nanocarrier for Prostate Cancer |
title | Development, Optimization and Evaluation of 2-Methoxy-Estradiol Loaded Nanocarrier for Prostate Cancer |
title_full | Development, Optimization and Evaluation of 2-Methoxy-Estradiol Loaded Nanocarrier for Prostate Cancer |
title_fullStr | Development, Optimization and Evaluation of 2-Methoxy-Estradiol Loaded Nanocarrier for Prostate Cancer |
title_full_unstemmed | Development, Optimization and Evaluation of 2-Methoxy-Estradiol Loaded Nanocarrier for Prostate Cancer |
title_short | Development, Optimization and Evaluation of 2-Methoxy-Estradiol Loaded Nanocarrier for Prostate Cancer |
title_sort | development, optimization and evaluation of 2-methoxy-estradiol loaded nanocarrier for prostate cancer |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322574/ https://www.ncbi.nlm.nih.gov/pubmed/34335251 http://dx.doi.org/10.3389/fphar.2021.682337 |
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