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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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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. |
format | Online Article Text |
id | pubmed-3603901 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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