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Bioinspired Composite, pH-Responsive Sodium Deoxycholate Hydrogel and Generation 4.5 Poly(amidoamine) Dendrimer Improves Cancer Treatment Efficacy via Doxorubicin and Resveratrol Co-Delivery

Maximizing the antitumor efficacy of doxorubicin (DOX) with a new drug delivery strategy is always desired in the field of biomedical science. Because the clinical applications of DOX in the treatment of cancer is limited by the side effects related to the dose. Herein, we report the co-loading of D...

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Autores principales: Mekonnen, Tefera Worku, Andrgie, Abegaz Tizazu, Darge, Haile Fentahun, Birhan, Yihenew Simegniew, Hanurry, Endiries Yibru, Chou, Hsiao-Ying, Lai, Juin-Yih, Tsai, Hsieh-Chih, Yang, Jen Ming, Chang, Yen-Hsiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696475/
https://www.ncbi.nlm.nih.gov/pubmed/33182410
http://dx.doi.org/10.3390/pharmaceutics12111069
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author Mekonnen, Tefera Worku
Andrgie, Abegaz Tizazu
Darge, Haile Fentahun
Birhan, Yihenew Simegniew
Hanurry, Endiries Yibru
Chou, Hsiao-Ying
Lai, Juin-Yih
Tsai, Hsieh-Chih
Yang, Jen Ming
Chang, Yen-Hsiang
author_facet Mekonnen, Tefera Worku
Andrgie, Abegaz Tizazu
Darge, Haile Fentahun
Birhan, Yihenew Simegniew
Hanurry, Endiries Yibru
Chou, Hsiao-Ying
Lai, Juin-Yih
Tsai, Hsieh-Chih
Yang, Jen Ming
Chang, Yen-Hsiang
author_sort Mekonnen, Tefera Worku
collection PubMed
description Maximizing the antitumor efficacy of doxorubicin (DOX) with a new drug delivery strategy is always desired in the field of biomedical science. Because the clinical applications of DOX in the treatment of cancer is limited by the side effects related to the dose. Herein, we report the co-loading of DOX and resveratrol (RESV) using an injectable in situ formed sodium deoxycholate hydrogel (Na-DOC-hyd) at the pH of the tumor extracellular microenvironment. The sequential, controlled, and sustained release of RESV and DOX for synergistic antitumor effects was confirmed by entrapping G4.5-DOX in the RESV-loaded Na-DOC hydrogel (Na-DOC-hyd-RESV). The synergistic antitumor activity of Na-DOC-hyd-RESV+G4.5-DOX was assessed on HeLa cell xenograft tumor in BALB/c nude mice. In the MTT biocompatibility assay, both the G4.5 PAMAM dendrimer and Na-DOC-hyd exhibited negligible cytotoxicity up to the highest dose of 2.0 mg mL(−1) in HeLa, MDA-MB-231, and HaCaT cells. The release profiles of DOX and RESV from the Na-DOC-hyd-RESV+G4.5-DOX confirmed the relatively rapid release of RESV (70.43 ± 1.39%), followed by that of DOX (54.58 ± 0.62%) at pH 6.5 in the 7 days of drug release studies. A single intratumoral injection of Na-DOC-hyd-RESV+G4.5-DOX maximally suppressed tumor growth during the 28 days of the treatment period. Na-DOC-hyd-RESV+G4.5-DOX did not cause any histological damage in the major visceral organs. Therefore, this Na-DOC-hydrogel for dual drugs (DOX and RESV) delivery at the pH of the tumor extracellular microenvironment is a promising, safe, and effective combination for antitumor chemotherapy.
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spelling pubmed-76964752020-11-29 Bioinspired Composite, pH-Responsive Sodium Deoxycholate Hydrogel and Generation 4.5 Poly(amidoamine) Dendrimer Improves Cancer Treatment Efficacy via Doxorubicin and Resveratrol Co-Delivery Mekonnen, Tefera Worku Andrgie, Abegaz Tizazu Darge, Haile Fentahun Birhan, Yihenew Simegniew Hanurry, Endiries Yibru Chou, Hsiao-Ying Lai, Juin-Yih Tsai, Hsieh-Chih Yang, Jen Ming Chang, Yen-Hsiang Pharmaceutics Article Maximizing the antitumor efficacy of doxorubicin (DOX) with a new drug delivery strategy is always desired in the field of biomedical science. Because the clinical applications of DOX in the treatment of cancer is limited by the side effects related to the dose. Herein, we report the co-loading of DOX and resveratrol (RESV) using an injectable in situ formed sodium deoxycholate hydrogel (Na-DOC-hyd) at the pH of the tumor extracellular microenvironment. The sequential, controlled, and sustained release of RESV and DOX for synergistic antitumor effects was confirmed by entrapping G4.5-DOX in the RESV-loaded Na-DOC hydrogel (Na-DOC-hyd-RESV). The synergistic antitumor activity of Na-DOC-hyd-RESV+G4.5-DOX was assessed on HeLa cell xenograft tumor in BALB/c nude mice. In the MTT biocompatibility assay, both the G4.5 PAMAM dendrimer and Na-DOC-hyd exhibited negligible cytotoxicity up to the highest dose of 2.0 mg mL(−1) in HeLa, MDA-MB-231, and HaCaT cells. The release profiles of DOX and RESV from the Na-DOC-hyd-RESV+G4.5-DOX confirmed the relatively rapid release of RESV (70.43 ± 1.39%), followed by that of DOX (54.58 ± 0.62%) at pH 6.5 in the 7 days of drug release studies. A single intratumoral injection of Na-DOC-hyd-RESV+G4.5-DOX maximally suppressed tumor growth during the 28 days of the treatment period. Na-DOC-hyd-RESV+G4.5-DOX did not cause any histological damage in the major visceral organs. Therefore, this Na-DOC-hydrogel for dual drugs (DOX and RESV) delivery at the pH of the tumor extracellular microenvironment is a promising, safe, and effective combination for antitumor chemotherapy. MDPI 2020-11-09 /pmc/articles/PMC7696475/ /pubmed/33182410 http://dx.doi.org/10.3390/pharmaceutics12111069 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mekonnen, Tefera Worku
Andrgie, Abegaz Tizazu
Darge, Haile Fentahun
Birhan, Yihenew Simegniew
Hanurry, Endiries Yibru
Chou, Hsiao-Ying
Lai, Juin-Yih
Tsai, Hsieh-Chih
Yang, Jen Ming
Chang, Yen-Hsiang
Bioinspired Composite, pH-Responsive Sodium Deoxycholate Hydrogel and Generation 4.5 Poly(amidoamine) Dendrimer Improves Cancer Treatment Efficacy via Doxorubicin and Resveratrol Co-Delivery
title Bioinspired Composite, pH-Responsive Sodium Deoxycholate Hydrogel and Generation 4.5 Poly(amidoamine) Dendrimer Improves Cancer Treatment Efficacy via Doxorubicin and Resveratrol Co-Delivery
title_full Bioinspired Composite, pH-Responsive Sodium Deoxycholate Hydrogel and Generation 4.5 Poly(amidoamine) Dendrimer Improves Cancer Treatment Efficacy via Doxorubicin and Resveratrol Co-Delivery
title_fullStr Bioinspired Composite, pH-Responsive Sodium Deoxycholate Hydrogel and Generation 4.5 Poly(amidoamine) Dendrimer Improves Cancer Treatment Efficacy via Doxorubicin and Resveratrol Co-Delivery
title_full_unstemmed Bioinspired Composite, pH-Responsive Sodium Deoxycholate Hydrogel and Generation 4.5 Poly(amidoamine) Dendrimer Improves Cancer Treatment Efficacy via Doxorubicin and Resveratrol Co-Delivery
title_short Bioinspired Composite, pH-Responsive Sodium Deoxycholate Hydrogel and Generation 4.5 Poly(amidoamine) Dendrimer Improves Cancer Treatment Efficacy via Doxorubicin and Resveratrol Co-Delivery
title_sort bioinspired composite, ph-responsive sodium deoxycholate hydrogel and generation 4.5 poly(amidoamine) dendrimer improves cancer treatment efficacy via doxorubicin and resveratrol co-delivery
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696475/
https://www.ncbi.nlm.nih.gov/pubmed/33182410
http://dx.doi.org/10.3390/pharmaceutics12111069
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