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Redox-sensitive micelles for targeted intracellular delivery and combination chemotherapy of paclitaxel and all-trans-retinoid acid
The application of paclitaxel (PTX) in clinic has been restricted due to its poor solubility. Several traditional nano-medicines have been developed to improve this defect, while they are still lack of tumor targeting ability and rapid drug release. In this work, an amphiphilic polymeric micelle of...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Shenyang Pharmaceutical University
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7032146/ https://www.ncbi.nlm.nih.gov/pubmed/32104480 http://dx.doi.org/10.1016/j.ajps.2018.08.009 |
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author | Han, Lingfei Hu, Lejian Liu, Fulei Wang, Xin Huang, Xiaoxian Liu, Bowen Feng, Feng Liu, Wenyuan Qu, Wei |
author_facet | Han, Lingfei Hu, Lejian Liu, Fulei Wang, Xin Huang, Xiaoxian Liu, Bowen Feng, Feng Liu, Wenyuan Qu, Wei |
author_sort | Han, Lingfei |
collection | PubMed |
description | The application of paclitaxel (PTX) in clinic has been restricted due to its poor solubility. Several traditional nano-medicines have been developed to improve this defect, while they are still lack of tumor targeting ability and rapid drug release. In this work, an amphiphilic polymeric micelle of hyaluronic acid (HA) – all-trans-retinoid acid (ATRA) with a disulfide bond, was developed successfully for the co-delivery of PTX and ATRA. The combination chemotherapy of PTX and ATRA can strengthen the anti-tumor activity. Along with self-assembling to micelles in water, the delivery system displayed satisfying drug loading capacities for both PTX (32.62% ± 1.39%) and ATRA, due to directly using ATRA as the hydrophobic group. Rapid drug release properties of the PTX-loaded redox-sensitive micelles (HA-SS-ATRA) in vitro were confirmed under reducing condition containing GSH. Besides, HA-CD44 mediated endocytosis promoted the uptake of HA-SS-ATRA micelles by B16F10 cells. Due to these properties, cytotoxicity assay verified that PTX-loaded HA-SS-ATRA micelles showed concentration-dependent cytotoxicity and displayed obvious combination therapy of PTX and ATRA. Importantly, HA-SS-ATRA micelles could remarkably prolong plasma circulation time after intravenously administration. Therefore, redox-sensitive HA-SS-ATRA micelles could be utilized and explored as a promising drug delivery system for cancer combination chemotherapy. |
format | Online Article Text |
id | pubmed-7032146 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Shenyang Pharmaceutical University |
record_format | MEDLINE/PubMed |
spelling | pubmed-70321462020-02-26 Redox-sensitive micelles for targeted intracellular delivery and combination chemotherapy of paclitaxel and all-trans-retinoid acid Han, Lingfei Hu, Lejian Liu, Fulei Wang, Xin Huang, Xiaoxian Liu, Bowen Feng, Feng Liu, Wenyuan Qu, Wei Asian J Pharm Sci Original Research Paper The application of paclitaxel (PTX) in clinic has been restricted due to its poor solubility. Several traditional nano-medicines have been developed to improve this defect, while they are still lack of tumor targeting ability and rapid drug release. In this work, an amphiphilic polymeric micelle of hyaluronic acid (HA) – all-trans-retinoid acid (ATRA) with a disulfide bond, was developed successfully for the co-delivery of PTX and ATRA. The combination chemotherapy of PTX and ATRA can strengthen the anti-tumor activity. Along with self-assembling to micelles in water, the delivery system displayed satisfying drug loading capacities for both PTX (32.62% ± 1.39%) and ATRA, due to directly using ATRA as the hydrophobic group. Rapid drug release properties of the PTX-loaded redox-sensitive micelles (HA-SS-ATRA) in vitro were confirmed under reducing condition containing GSH. Besides, HA-CD44 mediated endocytosis promoted the uptake of HA-SS-ATRA micelles by B16F10 cells. Due to these properties, cytotoxicity assay verified that PTX-loaded HA-SS-ATRA micelles showed concentration-dependent cytotoxicity and displayed obvious combination therapy of PTX and ATRA. Importantly, HA-SS-ATRA micelles could remarkably prolong plasma circulation time after intravenously administration. Therefore, redox-sensitive HA-SS-ATRA micelles could be utilized and explored as a promising drug delivery system for cancer combination chemotherapy. Shenyang Pharmaceutical University 2019-09 2018-09-24 /pmc/articles/PMC7032146/ /pubmed/32104480 http://dx.doi.org/10.1016/j.ajps.2018.08.009 Text en © 2018 Shenyang Pharmaceutical University. Published by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Research Paper Han, Lingfei Hu, Lejian Liu, Fulei Wang, Xin Huang, Xiaoxian Liu, Bowen Feng, Feng Liu, Wenyuan Qu, Wei Redox-sensitive micelles for targeted intracellular delivery and combination chemotherapy of paclitaxel and all-trans-retinoid acid |
title | Redox-sensitive micelles for targeted intracellular delivery and combination chemotherapy of paclitaxel and all-trans-retinoid acid |
title_full | Redox-sensitive micelles for targeted intracellular delivery and combination chemotherapy of paclitaxel and all-trans-retinoid acid |
title_fullStr | Redox-sensitive micelles for targeted intracellular delivery and combination chemotherapy of paclitaxel and all-trans-retinoid acid |
title_full_unstemmed | Redox-sensitive micelles for targeted intracellular delivery and combination chemotherapy of paclitaxel and all-trans-retinoid acid |
title_short | Redox-sensitive micelles for targeted intracellular delivery and combination chemotherapy of paclitaxel and all-trans-retinoid acid |
title_sort | redox-sensitive micelles for targeted intracellular delivery and combination chemotherapy of paclitaxel and all-trans-retinoid acid |
topic | Original Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7032146/ https://www.ncbi.nlm.nih.gov/pubmed/32104480 http://dx.doi.org/10.1016/j.ajps.2018.08.009 |
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