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Transporting Antitumor Drug Tamoxifen and Its Metabolites, 4-Hydroxytamoxifen and Endoxifen by Chitosan Nanoparticles

Synthetic and natural polymers are often used as drug delivery systems in vitro and in vivo. Biodegradable chitosan of different sizes were used to encapsulate antitumor drug tamoxifen (Tam) and its metabolites 4-hydroxytamoxifen (4-Hydroxytam) and endoxifen (Endox). The interactions of tamoxifen an...

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Autores principales: Agudelo, Daniel, Sanyakamdhorn, Sriwanna, Nafisi, Shoherh, Tajmir-Riahi, Heidar-Ali
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3603901/
https://www.ncbi.nlm.nih.gov/pubmed/23527310
http://dx.doi.org/10.1371/journal.pone.0060250
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author Agudelo, Daniel
Sanyakamdhorn, Sriwanna
Nafisi, Shoherh
Tajmir-Riahi, Heidar-Ali
author_facet Agudelo, Daniel
Sanyakamdhorn, Sriwanna
Nafisi, Shoherh
Tajmir-Riahi, Heidar-Ali
author_sort Agudelo, Daniel
collection PubMed
description Synthetic and natural polymers are often used as drug delivery systems in vitro and in vivo. Biodegradable chitosan of different sizes were used to encapsulate antitumor drug tamoxifen (Tam) and its metabolites 4-hydroxytamoxifen (4-Hydroxytam) and endoxifen (Endox). The interactions of tamoxifen and its metabolites with chitosan 15, 100 and 200 KD were investigated in aqueous solution, using FTIR, fluorescence spectroscopic methods and molecular modeling. The structural analysis showed that tamoxifen and its metabolites bind chitosan via both hydrophilic and hydrophobic contacts with overall binding constants of K (tam-ch-15)  = 8.7 (±0.5)×10(3) M(−1), K (tam-ch-100)  = 5.9 (±0.4)×10(5) M(−1), K (tam-ch-200)  = 2.4 (±0.4)×10(5) M(−1) and K (hydroxytam-ch-15)  = 2.6(±0.3)×10(4) M(−1), K (hydroxytam – ch-100)  = 5.2 (±0.7)×10(6) M(−1) and K (hydroxytam-ch-200)  = 5.1 (±0.5)×10(5) M(−1), K (endox-ch-15)  = 4.1 (±0.4)×10(3) M(−1), K (endox-ch-100)  = 1.2 (±0.3)×10(6) M(−1) and K (endox-ch-200)  = 4.7 (±0.5)×10(5) M(−1) with the number of drug molecules bound per chitosan (n) 2.8 to 0.5. The order of binding is ch-100>200>15 KD with stronger complexes formed with 4-hydroxytamoxifen than tamoxifen and endoxifen. The molecular modeling showed the participation of polymer charged NH(2) residues with drug OH and NH(2) groups in the drug-polymer adducts. The free binding energies of −3.46 kcal/mol for tamoxifen, −3.54 kcal/mol for 4-hydroxytamoxifen and −3.47 kcal/mol for endoxifen were estimated for these drug-polymer complexes. The results show chitosan 100 KD is stronger carrier for drug delivery than chitosan-15 and chitosan-200 KD.
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spelling pubmed-36039012013-03-22 Transporting Antitumor Drug Tamoxifen and Its Metabolites, 4-Hydroxytamoxifen and Endoxifen by Chitosan Nanoparticles Agudelo, Daniel Sanyakamdhorn, Sriwanna Nafisi, Shoherh Tajmir-Riahi, Heidar-Ali PLoS One Research Article Synthetic and natural polymers are often used as drug delivery systems in vitro and in vivo. Biodegradable chitosan of different sizes were used to encapsulate antitumor drug tamoxifen (Tam) and its metabolites 4-hydroxytamoxifen (4-Hydroxytam) and endoxifen (Endox). The interactions of tamoxifen and its metabolites with chitosan 15, 100 and 200 KD were investigated in aqueous solution, using FTIR, fluorescence spectroscopic methods and molecular modeling. The structural analysis showed that tamoxifen and its metabolites bind chitosan via both hydrophilic and hydrophobic contacts with overall binding constants of K (tam-ch-15)  = 8.7 (±0.5)×10(3) M(−1), K (tam-ch-100)  = 5.9 (±0.4)×10(5) M(−1), K (tam-ch-200)  = 2.4 (±0.4)×10(5) M(−1) and K (hydroxytam-ch-15)  = 2.6(±0.3)×10(4) M(−1), K (hydroxytam – ch-100)  = 5.2 (±0.7)×10(6) M(−1) and K (hydroxytam-ch-200)  = 5.1 (±0.5)×10(5) M(−1), K (endox-ch-15)  = 4.1 (±0.4)×10(3) M(−1), K (endox-ch-100)  = 1.2 (±0.3)×10(6) M(−1) and K (endox-ch-200)  = 4.7 (±0.5)×10(5) M(−1) with the number of drug molecules bound per chitosan (n) 2.8 to 0.5. The order of binding is ch-100>200>15 KD with stronger complexes formed with 4-hydroxytamoxifen than tamoxifen and endoxifen. The molecular modeling showed the participation of polymer charged NH(2) residues with drug OH and NH(2) groups in the drug-polymer adducts. The free binding energies of −3.46 kcal/mol for tamoxifen, −3.54 kcal/mol for 4-hydroxytamoxifen and −3.47 kcal/mol for endoxifen were estimated for these drug-polymer complexes. The results show chitosan 100 KD is stronger carrier for drug delivery than chitosan-15 and chitosan-200 KD. Public Library of Science 2013-03-20 /pmc/articles/PMC3603901/ /pubmed/23527310 http://dx.doi.org/10.1371/journal.pone.0060250 Text en © 2013 Agudelo et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Agudelo, Daniel
Sanyakamdhorn, Sriwanna
Nafisi, Shoherh
Tajmir-Riahi, Heidar-Ali
Transporting Antitumor Drug Tamoxifen and Its Metabolites, 4-Hydroxytamoxifen and Endoxifen by Chitosan Nanoparticles
title Transporting Antitumor Drug Tamoxifen and Its Metabolites, 4-Hydroxytamoxifen and Endoxifen by Chitosan Nanoparticles
title_full Transporting Antitumor Drug Tamoxifen and Its Metabolites, 4-Hydroxytamoxifen and Endoxifen by Chitosan Nanoparticles
title_fullStr Transporting Antitumor Drug Tamoxifen and Its Metabolites, 4-Hydroxytamoxifen and Endoxifen by Chitosan Nanoparticles
title_full_unstemmed Transporting Antitumor Drug Tamoxifen and Its Metabolites, 4-Hydroxytamoxifen and Endoxifen by Chitosan Nanoparticles
title_short Transporting Antitumor Drug Tamoxifen and Its Metabolites, 4-Hydroxytamoxifen and Endoxifen by Chitosan Nanoparticles
title_sort transporting antitumor drug tamoxifen and its metabolites, 4-hydroxytamoxifen and endoxifen by chitosan nanoparticles
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3603901/
https://www.ncbi.nlm.nih.gov/pubmed/23527310
http://dx.doi.org/10.1371/journal.pone.0060250
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