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Irinotecan-encapsulated double-reverse thermosensitive nanocarrier system for rectal administration

Intravenously administered for the treatment of rectum cancer, irinotecan produces severe side effects due to very high plasma concentrations. A novel irinotecan-encapsulated double reverse thermosensitive nanocarrier system (DRTN) for rectal administration was developed as an alternative. The DRTN...

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Autores principales: Din, Fakhar ud, Choi, Ju Yeon, Kim, Dong Wuk, Mustapha, Omer, Kim, Dong Shik, Thapa, Raj Kumar, Ku, Sae Kwang, Youn, Yu Seok, Oh, Kyung Taek, Yong, Chul Soon, Kim, Jong Oh, Choi, Han-Gon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241086/
https://www.ncbi.nlm.nih.gov/pubmed/28181835
http://dx.doi.org/10.1080/10717544.2016.1272651
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author Din, Fakhar ud
Choi, Ju Yeon
Kim, Dong Wuk
Mustapha, Omer
Kim, Dong Shik
Thapa, Raj Kumar
Ku, Sae Kwang
Youn, Yu Seok
Oh, Kyung Taek
Yong, Chul Soon
Kim, Jong Oh
Choi, Han-Gon
author_facet Din, Fakhar ud
Choi, Ju Yeon
Kim, Dong Wuk
Mustapha, Omer
Kim, Dong Shik
Thapa, Raj Kumar
Ku, Sae Kwang
Youn, Yu Seok
Oh, Kyung Taek
Yong, Chul Soon
Kim, Jong Oh
Choi, Han-Gon
author_sort Din, Fakhar ud
collection PubMed
description Intravenously administered for the treatment of rectum cancer, irinotecan produces severe side effects due to very high plasma concentrations. A novel irinotecan-encapsulated double reverse thermosensitive nanocarrier system (DRTN) for rectal administration was developed as an alternative. The DRTN was fabricated by dispersing the thermosensitive irinotecan-encapsulated solid lipid nanoparticles (SLN) in the thermosensitive poloxamer solution. Its gel properties, pharmacokinetics, morphology, anticancer activity and immunohistopathology were assessed after its rectal administration to rats and tumor-bearing mice. In the DRTN, the solid form of the SLN and the liquid form of the poloxamer solution persisted at 25 °C; the former melted to liquid, and the latter altered to gel at 36.5 °C. The DRTN was easily administered to the anus, gelling rapidly and strongly after rectal administration. Compared to the conventional hydrogel and intravenously administered solution, it retarded dissolution and initial plasma concentration. The DRTN gave sustained release and nearly constant plasma concentrations of irinotecan at 1–3 h in rats, resulting in improved anticancer activity. It induced no damage to the rat rectum and no body weight loss in tumor-bearing mice. Thus, this irinotecan-encapsulated DRTN associated with a reduced burst effect, lack of toxicity and excellent antitumor efficacy would be strongly recommended as a rectal pharmaceutical product alternative to commercial intravenous injection in the treatment of rectum and colon cancer.
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spelling pubmed-82410862021-07-08 Irinotecan-encapsulated double-reverse thermosensitive nanocarrier system for rectal administration Din, Fakhar ud Choi, Ju Yeon Kim, Dong Wuk Mustapha, Omer Kim, Dong Shik Thapa, Raj Kumar Ku, Sae Kwang Youn, Yu Seok Oh, Kyung Taek Yong, Chul Soon Kim, Jong Oh Choi, Han-Gon Drug Deliv Research Article Intravenously administered for the treatment of rectum cancer, irinotecan produces severe side effects due to very high plasma concentrations. A novel irinotecan-encapsulated double reverse thermosensitive nanocarrier system (DRTN) for rectal administration was developed as an alternative. The DRTN was fabricated by dispersing the thermosensitive irinotecan-encapsulated solid lipid nanoparticles (SLN) in the thermosensitive poloxamer solution. Its gel properties, pharmacokinetics, morphology, anticancer activity and immunohistopathology were assessed after its rectal administration to rats and tumor-bearing mice. In the DRTN, the solid form of the SLN and the liquid form of the poloxamer solution persisted at 25 °C; the former melted to liquid, and the latter altered to gel at 36.5 °C. The DRTN was easily administered to the anus, gelling rapidly and strongly after rectal administration. Compared to the conventional hydrogel and intravenously administered solution, it retarded dissolution and initial plasma concentration. The DRTN gave sustained release and nearly constant plasma concentrations of irinotecan at 1–3 h in rats, resulting in improved anticancer activity. It induced no damage to the rat rectum and no body weight loss in tumor-bearing mice. Thus, this irinotecan-encapsulated DRTN associated with a reduced burst effect, lack of toxicity and excellent antitumor efficacy would be strongly recommended as a rectal pharmaceutical product alternative to commercial intravenous injection in the treatment of rectum and colon cancer. Taylor & Francis 2017-02-09 /pmc/articles/PMC8241086/ /pubmed/28181835 http://dx.doi.org/10.1080/10717544.2016.1272651 Text en © 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Din, Fakhar ud
Choi, Ju Yeon
Kim, Dong Wuk
Mustapha, Omer
Kim, Dong Shik
Thapa, Raj Kumar
Ku, Sae Kwang
Youn, Yu Seok
Oh, Kyung Taek
Yong, Chul Soon
Kim, Jong Oh
Choi, Han-Gon
Irinotecan-encapsulated double-reverse thermosensitive nanocarrier system for rectal administration
title Irinotecan-encapsulated double-reverse thermosensitive nanocarrier system for rectal administration
title_full Irinotecan-encapsulated double-reverse thermosensitive nanocarrier system for rectal administration
title_fullStr Irinotecan-encapsulated double-reverse thermosensitive nanocarrier system for rectal administration
title_full_unstemmed Irinotecan-encapsulated double-reverse thermosensitive nanocarrier system for rectal administration
title_short Irinotecan-encapsulated double-reverse thermosensitive nanocarrier system for rectal administration
title_sort irinotecan-encapsulated double-reverse thermosensitive nanocarrier system for rectal administration
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241086/
https://www.ncbi.nlm.nih.gov/pubmed/28181835
http://dx.doi.org/10.1080/10717544.2016.1272651
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