Carboxylic Acid- and Amine-Modified Pluronic F127-Based Thermoresponsive Nanogels as Smart Carriers for Brain Drug Delivery

Abegaz Tizazu Andrgie,1 Cheng-Han Liao,2 Tsung-Yun Wu,2,3 Hsueh-Hui Yang,4 Horng-Jyh Harn,5,6 Shinn-Zong Lin,5,7 Yu-Shuan Chen,4,5,8 Hsieh-Chih Tsai2,3,9 1Department of Biotechnology, Debre Berhan University, Debre Berhan, Ethiopia; 2Graduate Institute of Applied Science and Technology, National Tai...

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Main Authors: Andrgie AT, Liao CH, Wu TY, Yang HH, Harn HJ, Lin SZ, Chen YS, Tsai HC
Format: Article
Language:English
Published: Dove Medical Press 2025-05-01
Series:International Journal of Nanomedicine
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Online Access:https://www.dovepress.com/carboxylic-acid--and-amine-modified-pluronic-f127-based-thermoresponsi-peer-reviewed-fulltext-article-IJN
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author Andrgie AT
Liao CH
Wu TY
Yang HH
Harn HJ
Lin SZ
Chen YS
Tsai HC
author_facet Andrgie AT
Liao CH
Wu TY
Yang HH
Harn HJ
Lin SZ
Chen YS
Tsai HC
author_sort Andrgie AT
collection DOAJ
description Abegaz Tizazu Andrgie,1 Cheng-Han Liao,2 Tsung-Yun Wu,2,3 Hsueh-Hui Yang,4 Horng-Jyh Harn,5,6 Shinn-Zong Lin,5,7 Yu-Shuan Chen,4,5,8 Hsieh-Chih Tsai2,3,9 1Department of Biotechnology, Debre Berhan University, Debre Berhan, Ethiopia; 2Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei, 106, Taiwan, Republic of China; 3Advanced Membrane Materials Center, National Taiwan University of Science and Technology, Taipei, 106, Taiwan; 4Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, 970, Taiwan; 5Bioinnovation Center, Buddhist Tzu Chi Medical Foundation, Hualien, 970, Taiwan; 6Department of Pathology, Hualien Tzu Chi Hospital, Tzu Chi University, Buddhist Tzu Chi Medical Foundation, Hualien, 970, Taiwan; 7Department of Neurosurgery, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, 970, Taiwan; 8Center for General Education, Tzu Chi University, Hualien, 970, Taiwan; 9R&D Center for Membrane Technology, Chung Yuan Christian University, Taoyuan, 320, TaiwanCorrespondence: Yu-Shuan Chen, Email yushuanchenxie@gmail.com Hsieh-Chih Tsai, Email h.c.tsai@mail.ntust.edu.twIntroduction: The blood-brain barrier (BBB) is a critical protective barrier that regulates the exchange of substances between the circulatory system and brain, restricting the access of drugs to brain tissues. Developing novel delivery strategies across the BBB is challenging but crucial. Multifunctional nanogels are promising drug carriers for delivering therapeutic agents to their intended target areas in the brain tissue.Methods: This study introduced carboxylic acid- and amine-modified Pluronic F127 (ADF127 and EDF127)-based thermoresponsive nanogel systems as drug nanocarriers for brain tissues. The release profiles of 3-butylidenephthalide (BP) from the nanogels were investigated in vitro in phosphate-buffered saline (pH 7.4) at 37 °C for 48 h. Additionally, the accumulation of DiR-labeled nanogels in vital organs was observed using fluorescence imaging.Results: A relatively sustained BP release (27%) from ADF127, followed by rapid BP release (39%) from Pluronic F127 within the first 4 h were observed. In vivo studies using the C57BL/6JNarl mouse model showed that intravenously administered BP-loaded copolymeric nanogels exhibited a rapid BP distribution to the liver, spleen, heart, and kidney. DiR fluorescence intensity in the brain increased in the order Pluronic F127 < ADF127 < EDF127 copolymeric nanogels. Although the fluorescence intensity of DiR in the brain tissue was relatively lower than those in other vital organs, the DiR-labeled EDF127 copolymeric nanogels showed approximately 10-fold higher fluorescence intensity.Conclusion: Positively charged drug carrier nanomaterials demonstrate a higher propensity for transfer through the BBB, significantly expanding the applicability of positively charged EDF127 nanogels as nanocarriers for in vivo brain tissue treatment and imaging. Therefore, owing to their increased permeability across the BBB, carboxylic acid- and amine-modified Pluronic F127 nanogels (EDF127 and ADF127) will also offer a promising approach for brain tissue treatment and imaging.Keywords: blood-brain barrier, DiR labeling, permeability, sustained release, nanogels
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spelling doaj-art-8361ba94deb842c48272730eeed545d82025-08-20T03:53:11ZengDove Medical PressInternational Journal of Nanomedicine1178-20132025-05-01Volume 20Issue 158935905102757Carboxylic Acid- and Amine-Modified Pluronic F127-Based Thermoresponsive Nanogels as Smart Carriers for Brain Drug DeliveryAndrgie AT0Liao CH1Wu TYYang HH2Harn HJ3Lin SZ4Chen YS5Tsai HC6Department of BiotechnologyGraduate Institute of Applied Science and TechnologyDepartment of Medical ResearchDepartment of PathologyDepartment of NeurosurgeryDepartment of Medical ResearchGraduate Institute of Applied Science and TechnologyAbegaz Tizazu Andrgie,1 Cheng-Han Liao,2 Tsung-Yun Wu,2,3 Hsueh-Hui Yang,4 Horng-Jyh Harn,5,6 Shinn-Zong Lin,5,7 Yu-Shuan Chen,4,5,8 Hsieh-Chih Tsai2,3,9 1Department of Biotechnology, Debre Berhan University, Debre Berhan, Ethiopia; 2Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei, 106, Taiwan, Republic of China; 3Advanced Membrane Materials Center, National Taiwan University of Science and Technology, Taipei, 106, Taiwan; 4Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, 970, Taiwan; 5Bioinnovation Center, Buddhist Tzu Chi Medical Foundation, Hualien, 970, Taiwan; 6Department of Pathology, Hualien Tzu Chi Hospital, Tzu Chi University, Buddhist Tzu Chi Medical Foundation, Hualien, 970, Taiwan; 7Department of Neurosurgery, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, 970, Taiwan; 8Center for General Education, Tzu Chi University, Hualien, 970, Taiwan; 9R&D Center for Membrane Technology, Chung Yuan Christian University, Taoyuan, 320, TaiwanCorrespondence: Yu-Shuan Chen, Email yushuanchenxie@gmail.com Hsieh-Chih Tsai, Email h.c.tsai@mail.ntust.edu.twIntroduction: The blood-brain barrier (BBB) is a critical protective barrier that regulates the exchange of substances between the circulatory system and brain, restricting the access of drugs to brain tissues. Developing novel delivery strategies across the BBB is challenging but crucial. Multifunctional nanogels are promising drug carriers for delivering therapeutic agents to their intended target areas in the brain tissue.Methods: This study introduced carboxylic acid- and amine-modified Pluronic F127 (ADF127 and EDF127)-based thermoresponsive nanogel systems as drug nanocarriers for brain tissues. The release profiles of 3-butylidenephthalide (BP) from the nanogels were investigated in vitro in phosphate-buffered saline (pH 7.4) at 37 °C for 48 h. Additionally, the accumulation of DiR-labeled nanogels in vital organs was observed using fluorescence imaging.Results: A relatively sustained BP release (27%) from ADF127, followed by rapid BP release (39%) from Pluronic F127 within the first 4 h were observed. In vivo studies using the C57BL/6JNarl mouse model showed that intravenously administered BP-loaded copolymeric nanogels exhibited a rapid BP distribution to the liver, spleen, heart, and kidney. DiR fluorescence intensity in the brain increased in the order Pluronic F127 < ADF127 < EDF127 copolymeric nanogels. Although the fluorescence intensity of DiR in the brain tissue was relatively lower than those in other vital organs, the DiR-labeled EDF127 copolymeric nanogels showed approximately 10-fold higher fluorescence intensity.Conclusion: Positively charged drug carrier nanomaterials demonstrate a higher propensity for transfer through the BBB, significantly expanding the applicability of positively charged EDF127 nanogels as nanocarriers for in vivo brain tissue treatment and imaging. Therefore, owing to their increased permeability across the BBB, carboxylic acid- and amine-modified Pluronic F127 nanogels (EDF127 and ADF127) will also offer a promising approach for brain tissue treatment and imaging.Keywords: blood-brain barrier, DiR labeling, permeability, sustained release, nanogelshttps://www.dovepress.com/carboxylic-acid--and-amine-modified-pluronic-f127-based-thermoresponsi-peer-reviewed-fulltext-article-IJNblood-brain barrierDiR labelingpermeabilitysustained releasenanogels
spellingShingle Andrgie AT
Liao CH
Wu TY
Yang HH
Harn HJ
Lin SZ
Chen YS
Tsai HC
Carboxylic Acid- and Amine-Modified Pluronic F127-Based Thermoresponsive Nanogels as Smart Carriers for Brain Drug Delivery
International Journal of Nanomedicine
blood-brain barrier
DiR labeling
permeability
sustained release
nanogels
title Carboxylic Acid- and Amine-Modified Pluronic F127-Based Thermoresponsive Nanogels as Smart Carriers for Brain Drug Delivery
title_full Carboxylic Acid- and Amine-Modified Pluronic F127-Based Thermoresponsive Nanogels as Smart Carriers for Brain Drug Delivery
title_fullStr Carboxylic Acid- and Amine-Modified Pluronic F127-Based Thermoresponsive Nanogels as Smart Carriers for Brain Drug Delivery
title_full_unstemmed Carboxylic Acid- and Amine-Modified Pluronic F127-Based Thermoresponsive Nanogels as Smart Carriers for Brain Drug Delivery
title_short Carboxylic Acid- and Amine-Modified Pluronic F127-Based Thermoresponsive Nanogels as Smart Carriers for Brain Drug Delivery
title_sort carboxylic acid and amine modified pluronic f127 based thermoresponsive nanogels as smart carriers for brain drug delivery
topic blood-brain barrier
DiR labeling
permeability
sustained release
nanogels
url https://www.dovepress.com/carboxylic-acid--and-amine-modified-pluronic-f127-based-thermoresponsi-peer-reviewed-fulltext-article-IJN
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