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A Mixed Thermosensitive Hydrogel System for Sustained Delivery of Tacrolimus for Immunosuppressive Therapy
Tacrolimus is an immunosuppressive agent for acute rejection after allotransplantation. However, the low aqueous solubility of tacrolimus poses difficulties in formulating an injection dosage. Polypeptide thermosensitive hydrogels can maintain a sustained release depot to deliver tacrolimus. The cop...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723608/ https://www.ncbi.nlm.nih.gov/pubmed/31416239 http://dx.doi.org/10.3390/pharmaceutics11080413 |
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author | Lin, Hsiu-Chao Anggelia, Madonna Rica Cheng, Chih-Chi Ku, Kuan-Lin Cheng, Hui-Yun Wen, Chih-Jen Wang, Aline Yen Ling Lin, Cheng-Hung Chu, I-Ming |
author_facet | Lin, Hsiu-Chao Anggelia, Madonna Rica Cheng, Chih-Chi Ku, Kuan-Lin Cheng, Hui-Yun Wen, Chih-Jen Wang, Aline Yen Ling Lin, Cheng-Hung Chu, I-Ming |
author_sort | Lin, Hsiu-Chao |
collection | PubMed |
description | Tacrolimus is an immunosuppressive agent for acute rejection after allotransplantation. However, the low aqueous solubility of tacrolimus poses difficulties in formulating an injection dosage. Polypeptide thermosensitive hydrogels can maintain a sustained release depot to deliver tacrolimus. The copolymers, which consist of poloxamer and poly(l-alanine) with l-lysine segments at both ends (P–Lys–Ala–PLX), are able to carry tacrolimus in an in situ gelled form with acceptable biocompatibility, biodegradability, and low gelling concentrations from 3 to 7 wt %. By adding Pluronic F-127 to formulate a mixed hydrogel system, the drug release rate can be adjusted to maintain suitable drug levels in animals with transplants. Under this formulation, the in vitro release of tacrolimus was stable for more than 100 days, while in vivo release of tacrolimus in mouse model showed that rejection from skin allotransplantation was prevented for at least three weeks with one single administration. Using these mixed hydrogel systems for sustaining delivery of tacrolimus demonstrates advancement in immunosuppressive therapy. |
format | Online Article Text |
id | pubmed-6723608 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-67236082019-09-10 A Mixed Thermosensitive Hydrogel System for Sustained Delivery of Tacrolimus for Immunosuppressive Therapy Lin, Hsiu-Chao Anggelia, Madonna Rica Cheng, Chih-Chi Ku, Kuan-Lin Cheng, Hui-Yun Wen, Chih-Jen Wang, Aline Yen Ling Lin, Cheng-Hung Chu, I-Ming Pharmaceutics Article Tacrolimus is an immunosuppressive agent for acute rejection after allotransplantation. However, the low aqueous solubility of tacrolimus poses difficulties in formulating an injection dosage. Polypeptide thermosensitive hydrogels can maintain a sustained release depot to deliver tacrolimus. The copolymers, which consist of poloxamer and poly(l-alanine) with l-lysine segments at both ends (P–Lys–Ala–PLX), are able to carry tacrolimus in an in situ gelled form with acceptable biocompatibility, biodegradability, and low gelling concentrations from 3 to 7 wt %. By adding Pluronic F-127 to formulate a mixed hydrogel system, the drug release rate can be adjusted to maintain suitable drug levels in animals with transplants. Under this formulation, the in vitro release of tacrolimus was stable for more than 100 days, while in vivo release of tacrolimus in mouse model showed that rejection from skin allotransplantation was prevented for at least three weeks with one single administration. Using these mixed hydrogel systems for sustaining delivery of tacrolimus demonstrates advancement in immunosuppressive therapy. MDPI 2019-08-14 /pmc/articles/PMC6723608/ /pubmed/31416239 http://dx.doi.org/10.3390/pharmaceutics11080413 Text en © 2019 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 Lin, Hsiu-Chao Anggelia, Madonna Rica Cheng, Chih-Chi Ku, Kuan-Lin Cheng, Hui-Yun Wen, Chih-Jen Wang, Aline Yen Ling Lin, Cheng-Hung Chu, I-Ming A Mixed Thermosensitive Hydrogel System for Sustained Delivery of Tacrolimus for Immunosuppressive Therapy |
title | A Mixed Thermosensitive Hydrogel System for Sustained Delivery of Tacrolimus for Immunosuppressive Therapy |
title_full | A Mixed Thermosensitive Hydrogel System for Sustained Delivery of Tacrolimus for Immunosuppressive Therapy |
title_fullStr | A Mixed Thermosensitive Hydrogel System for Sustained Delivery of Tacrolimus for Immunosuppressive Therapy |
title_full_unstemmed | A Mixed Thermosensitive Hydrogel System for Sustained Delivery of Tacrolimus for Immunosuppressive Therapy |
title_short | A Mixed Thermosensitive Hydrogel System for Sustained Delivery of Tacrolimus for Immunosuppressive Therapy |
title_sort | mixed thermosensitive hydrogel system for sustained delivery of tacrolimus for immunosuppressive therapy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723608/ https://www.ncbi.nlm.nih.gov/pubmed/31416239 http://dx.doi.org/10.3390/pharmaceutics11080413 |
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