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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...

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Autores principales: Alhakamy, Nabil A., Ahmed, Osama A., Fahmy, Usama A., Asfour, Hani Z., Alghaith, Adel F., Mahdi, Wael A., Alshehri, Sultan, Md, Shadab
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
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.
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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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