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A pH responsive complexation-based drug delivery system for oxaliplatin
A responsive drug delivery system (DDS) for oxaliplatin (OX) has been designed with a view to overcoming several drawbacks associated with this anticancer agent, including fast degradation/deactivation in the blood stream, lack of tumor selectivity, and low bioavailability. The present approach is b...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Royal Society of Chemistry
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618340/ https://www.ncbi.nlm.nih.gov/pubmed/28970876 http://dx.doi.org/10.1039/c7sc01438d |
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author | Li, Bin Meng, Zhao Li, Qianqian Huang, Xiayang Kang, Ziyao Dong, Huajin Chen, Junyi Sun, Ji Dong, Yansheng Li, Jian Jia, Xueshun Sessler, Jonathan L. Meng, Qingbin Li, Chunju |
author_facet | Li, Bin Meng, Zhao Li, Qianqian Huang, Xiayang Kang, Ziyao Dong, Huajin Chen, Junyi Sun, Ji Dong, Yansheng Li, Jian Jia, Xueshun Sessler, Jonathan L. Meng, Qingbin Li, Chunju |
author_sort | Li, Bin |
collection | PubMed |
description | A responsive drug delivery system (DDS) for oxaliplatin (OX) has been designed with a view to overcoming several drawbacks associated with this anticancer agent, including fast degradation/deactivation in the blood stream, lack of tumor selectivity, and low bioavailability. The present approach is based on the direct host–guest encapsulation of OX by a pH-responsive receptor, carboxylatopillar[6]arene (CP6A). The binding affinities of CP6A for OX were found to be pH-sensitive at biologically relevant pH. For example, the association constant (K (a)) at pH 7.4 [K (a) = (1.02 ± 0.05) × 10(4) M(–1)] is 24 times larger than that at pH 5.4 [K (a) = (4.21 ± 0.06) × 10(2) M(–1)]. Encapsulation of OX within the CP6A cavity did not affect its in vitro cytotoxicity as inferred from comparison studies carried out in several cancer cells (e.g., the HepG-2, MCF-7, and A549 cell lines). On the other hand, complexation by CP6A serves to increase the inherent stability of OX in plasma by 2.8-fold over a 24 h incubation period. The formation of a CP6A⊃OX host–guest complex served to enhance in a statistically significant way the ability of OX to inhibit the regrowth of sarcoma 180 (S180) tumors in Kunming (KM) mice xenografts. The improved anticancer activity observed in vivo for CP6A⊃OX is attributed to the combined effects of enhanced stability of the host–guest complex and the pH-responsive release of OX. Specifically, it is proposed that OX is protected as the result of complex formation and then released effectively in the acidic tumor environment. |
format | Online Article Text |
id | pubmed-5618340 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-56183402017-10-02 A pH responsive complexation-based drug delivery system for oxaliplatin Li, Bin Meng, Zhao Li, Qianqian Huang, Xiayang Kang, Ziyao Dong, Huajin Chen, Junyi Sun, Ji Dong, Yansheng Li, Jian Jia, Xueshun Sessler, Jonathan L. Meng, Qingbin Li, Chunju Chem Sci Chemistry A responsive drug delivery system (DDS) for oxaliplatin (OX) has been designed with a view to overcoming several drawbacks associated with this anticancer agent, including fast degradation/deactivation in the blood stream, lack of tumor selectivity, and low bioavailability. The present approach is based on the direct host–guest encapsulation of OX by a pH-responsive receptor, carboxylatopillar[6]arene (CP6A). The binding affinities of CP6A for OX were found to be pH-sensitive at biologically relevant pH. For example, the association constant (K (a)) at pH 7.4 [K (a) = (1.02 ± 0.05) × 10(4) M(–1)] is 24 times larger than that at pH 5.4 [K (a) = (4.21 ± 0.06) × 10(2) M(–1)]. Encapsulation of OX within the CP6A cavity did not affect its in vitro cytotoxicity as inferred from comparison studies carried out in several cancer cells (e.g., the HepG-2, MCF-7, and A549 cell lines). On the other hand, complexation by CP6A serves to increase the inherent stability of OX in plasma by 2.8-fold over a 24 h incubation period. The formation of a CP6A⊃OX host–guest complex served to enhance in a statistically significant way the ability of OX to inhibit the regrowth of sarcoma 180 (S180) tumors in Kunming (KM) mice xenografts. The improved anticancer activity observed in vivo for CP6A⊃OX is attributed to the combined effects of enhanced stability of the host–guest complex and the pH-responsive release of OX. Specifically, it is proposed that OX is protected as the result of complex formation and then released effectively in the acidic tumor environment. Royal Society of Chemistry 2017-06-01 2017-04-19 /pmc/articles/PMC5618340/ /pubmed/28970876 http://dx.doi.org/10.1039/c7sc01438d Text en This journal is © The Royal Society of Chemistry 2017 http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Chemistry Li, Bin Meng, Zhao Li, Qianqian Huang, Xiayang Kang, Ziyao Dong, Huajin Chen, Junyi Sun, Ji Dong, Yansheng Li, Jian Jia, Xueshun Sessler, Jonathan L. Meng, Qingbin Li, Chunju A pH responsive complexation-based drug delivery system for oxaliplatin |
title | A pH responsive complexation-based drug delivery system for oxaliplatin
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title_full | A pH responsive complexation-based drug delivery system for oxaliplatin
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title_fullStr | A pH responsive complexation-based drug delivery system for oxaliplatin
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title_full_unstemmed | A pH responsive complexation-based drug delivery system for oxaliplatin
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title_short | A pH responsive complexation-based drug delivery system for oxaliplatin
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title_sort | ph responsive complexation-based drug delivery system for oxaliplatin |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618340/ https://www.ncbi.nlm.nih.gov/pubmed/28970876 http://dx.doi.org/10.1039/c7sc01438d |
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