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Development and optimization of sustained release triptolide microspheres
Rheumatoid arthritis is considered a chronic systemic autoimmune disorder that may cause joint destruction. Triptolide, an active component isolated from Tripterygium wilfordii Hook.f., is considered to have promising potential for clinical use in treating rheumatoid arthritis. However, its clinical...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10586653/ https://www.ncbi.nlm.nih.gov/pubmed/37856525 http://dx.doi.org/10.1371/journal.pone.0292861 |
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author | Zeng, Hui-lin Qiu, Qian Fu, Ting-xiong Deng, Ai-ping Xie, Xiang-yang |
author_facet | Zeng, Hui-lin Qiu, Qian Fu, Ting-xiong Deng, Ai-ping Xie, Xiang-yang |
author_sort | Zeng, Hui-lin |
collection | PubMed |
description | Rheumatoid arthritis is considered a chronic systemic autoimmune disorder that may cause joint destruction. Triptolide, an active component isolated from Tripterygium wilfordii Hook.f., is considered to have promising potential for clinical use in treating rheumatoid arthritis. However, its clinical application has been limited by the narrow therapeutic window, side effects associated with plasma drug fluctuations, low oral bioavailability, and poor patient compliance with the long and frequent dosing regimen. An extended drug release preparation may address these limitations. The aim of this work was therefore to develop, formulate and optimize sustained release triptolide microspheres with poly (lactide-co-glycolide) (PLGA). Triptolide-loaded microspheres were prepared using PLGA as the matrix polymer, dichloromethane as the oil phase, and polyvinyl alcohol (PVA) as the matrix forming emulsifier. An oil-in-water (O/W) emulsion solvent evaporation technique was utilized to prepare the microspheres. Surface response methodology (RSM) coupled with central composite design (CCD) was used to optimize the formulation and a total of twenty formulations were prepared. PVA concentration (X(1)), PLGA concentration (X(2)), and theoretical drug content (X(3)) were selected as independent variables; and drug content (Y(1)), encapsulation efficiency (Y(2)), mean diameter (Y(3)) and the initial release during the first day (Y(4)) were taken as the response variables. The optimized formulation showed mean diameter of 42.36 μm, drug content of 7.96%, encapsulation efficiency of 80.16% and an initial release of 14.48%. The prepared microspheres exhibited a sustained release profile of triptolide in vitro over 4 weeks, which was wellfitted with a Korsmeyer-Peppas equation. However, the initial drug release (~14%) of triptolide-loaded microspheres was very high and should be specifically investigated in future studies. The results indicate that long-term sustained release microspheres of triptolide can be considered a strategy to overcome the low bioavailability and poor patient compliance with conventional triptolide tablets. The issue of initial burst release and in vivo evaluations should be specifically investigated in the future. |
format | Online Article Text |
id | pubmed-10586653 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-105866532023-10-20 Development and optimization of sustained release triptolide microspheres Zeng, Hui-lin Qiu, Qian Fu, Ting-xiong Deng, Ai-ping Xie, Xiang-yang PLoS One Research Article Rheumatoid arthritis is considered a chronic systemic autoimmune disorder that may cause joint destruction. Triptolide, an active component isolated from Tripterygium wilfordii Hook.f., is considered to have promising potential for clinical use in treating rheumatoid arthritis. However, its clinical application has been limited by the narrow therapeutic window, side effects associated with plasma drug fluctuations, low oral bioavailability, and poor patient compliance with the long and frequent dosing regimen. An extended drug release preparation may address these limitations. The aim of this work was therefore to develop, formulate and optimize sustained release triptolide microspheres with poly (lactide-co-glycolide) (PLGA). Triptolide-loaded microspheres were prepared using PLGA as the matrix polymer, dichloromethane as the oil phase, and polyvinyl alcohol (PVA) as the matrix forming emulsifier. An oil-in-water (O/W) emulsion solvent evaporation technique was utilized to prepare the microspheres. Surface response methodology (RSM) coupled with central composite design (CCD) was used to optimize the formulation and a total of twenty formulations were prepared. PVA concentration (X(1)), PLGA concentration (X(2)), and theoretical drug content (X(3)) were selected as independent variables; and drug content (Y(1)), encapsulation efficiency (Y(2)), mean diameter (Y(3)) and the initial release during the first day (Y(4)) were taken as the response variables. The optimized formulation showed mean diameter of 42.36 μm, drug content of 7.96%, encapsulation efficiency of 80.16% and an initial release of 14.48%. The prepared microspheres exhibited a sustained release profile of triptolide in vitro over 4 weeks, which was wellfitted with a Korsmeyer-Peppas equation. However, the initial drug release (~14%) of triptolide-loaded microspheres was very high and should be specifically investigated in future studies. The results indicate that long-term sustained release microspheres of triptolide can be considered a strategy to overcome the low bioavailability and poor patient compliance with conventional triptolide tablets. The issue of initial burst release and in vivo evaluations should be specifically investigated in the future. Public Library of Science 2023-10-19 /pmc/articles/PMC10586653/ /pubmed/37856525 http://dx.doi.org/10.1371/journal.pone.0292861 Text en © 2023 Zeng et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Zeng, Hui-lin Qiu, Qian Fu, Ting-xiong Deng, Ai-ping Xie, Xiang-yang Development and optimization of sustained release triptolide microspheres |
title | Development and optimization of sustained release triptolide microspheres |
title_full | Development and optimization of sustained release triptolide microspheres |
title_fullStr | Development and optimization of sustained release triptolide microspheres |
title_full_unstemmed | Development and optimization of sustained release triptolide microspheres |
title_short | Development and optimization of sustained release triptolide microspheres |
title_sort | development and optimization of sustained release triptolide microspheres |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10586653/ https://www.ncbi.nlm.nih.gov/pubmed/37856525 http://dx.doi.org/10.1371/journal.pone.0292861 |
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