Treatment efficacy of low-dose 5-fluorouracil with ultrasound in mediating 5-fluorouracil-loaded microbubble cavitation in head and neck cancer

AbstractOver the past 50 years, 5-fluorouracil (5-FU) has played a critical role in the systemic chemotherapy of cancer patients. Bolus intravenous (IV) 5-FU infusion has been used due to the limitation of its extremely short half-life (10–15 min). This study used ultrasound (US) mediating 5-FU-load...

Full description

Bibliographic Details
Main Authors: Ai-Ho Liao, Yu-An Lee, Dao-Lung Lin, Ho-Chiao Chuang, Jehng-Kang Wang, Ching-En Chang, Hsiang-Tzu Li, Ting-Yi Wu, Cheng-Ping Shih, Chih-Hung Wang, Yueng-Hsiang Chu
Format: Article
Language:English
Published: Taylor & Francis Group 2023-12-01
Series:Drug Delivery
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/10717544.2022.2154410
_version_ 1797260950274834432
author Ai-Ho Liao
Yu-An Lee
Dao-Lung Lin
Ho-Chiao Chuang
Jehng-Kang Wang
Ching-En Chang
Hsiang-Tzu Li
Ting-Yi Wu
Cheng-Ping Shih
Chih-Hung Wang
Yueng-Hsiang Chu
author_facet Ai-Ho Liao
Yu-An Lee
Dao-Lung Lin
Ho-Chiao Chuang
Jehng-Kang Wang
Ching-En Chang
Hsiang-Tzu Li
Ting-Yi Wu
Cheng-Ping Shih
Chih-Hung Wang
Yueng-Hsiang Chu
author_sort Ai-Ho Liao
collection DOAJ
description AbstractOver the past 50 years, 5-fluorouracil (5-FU) has played a critical role in the systemic chemotherapy of cancer patients. Bolus intravenous (IV) 5-FU infusion has been used due to the limitation of its extremely short half-life (10–15 min). This study used ultrasound (US) mediating 5-FU-loaded microbubbles (MBs) cavitation as a tool to increase local intratumoral 5-FU levels with a reduced dose of 5-FU (a single IV injection of 2.5 mg/kg instead of a single intraperitoneal injection of 25–200 mg/kg as used in previous studies in mice). The 5-FU-MBs were prepared with a 132 mg/mL albumin solution and a 0.30 mg/mL 5-FU solution. The diameters of the MBs and 5-FU-MBs were 1.24 ± 0.85 and 2.00 ± 0.53 µm (mean ± SEM), respectively, and the maximum loading efficiency of 5-FU on MBs was 19.04 ± 0.25%. In the in vitro study, the cell viabilities of 5-FU and 5-FU-MBs did not differ significantly, but compared with the 5-FU-MBs treatment-alone group, cell toxicity increased to 31% in the 5-FU-MBs + US group (p < 0.001). The biodistribution results indicated that the 5-FU levels of the tumors in small animals were significant higher for the 5-FU-MBs + US treatment than for either the 5-FU-MBs or 5-FU treatment with low 5-FU systemic treatment doses (2.5 mg/kg 5-FU IV). In small-animal treatment, 2.5 mg/kg 5-FU therapeutic IV doses injected into mice caused a more-significant reduction in tumor growth in the 5-FU-MBs + US group (65.9%) than in the control group after 34 days of treatment.
first_indexed 2024-03-08T23:30:48Z
format Article
id doaj.art-872d9d03bf354cda85d87c19c1c81525
institution Directory Open Access Journal
issn 1071-7544
1521-0464
language English
last_indexed 2024-04-24T23:33:28Z
publishDate 2023-12-01
publisher Taylor & Francis Group
record_format Article
series Drug Delivery
spelling doaj.art-872d9d03bf354cda85d87c19c1c815252024-03-15T14:22:18ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642023-12-0130111310.1080/10717544.2022.2154410Treatment efficacy of low-dose 5-fluorouracil with ultrasound in mediating 5-fluorouracil-loaded microbubble cavitation in head and neck cancerAi-Ho Liao0Yu-An Lee1Dao-Lung Lin2Ho-Chiao Chuang3Jehng-Kang Wang4Ching-En Chang5Hsiang-Tzu Li6Ting-Yi Wu7Cheng-Ping Shih8Chih-Hung Wang9Yueng-Hsiang Chu10Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei, TaiwanGraduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei, TaiwanSpirit Scientific Co., Ltd, Taiwan Branch (Cayman), New Taipei City, TaiwanDepartment of Mechanical Engineering, National Taipei University of Technology, Taipei, TaiwanDepartment of Biochemistry, National Defense Medical Center, Taipei, TaiwanGraduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei, TaiwanGraduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei, TaiwanGraduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei, TaiwanDepartment of Otolaryngology–Head and Neck Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, TaiwanDepartment of Otolaryngology–Head and Neck Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, TaiwanDepartment of Otolaryngology–Head and Neck Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, TaiwanAbstractOver the past 50 years, 5-fluorouracil (5-FU) has played a critical role in the systemic chemotherapy of cancer patients. Bolus intravenous (IV) 5-FU infusion has been used due to the limitation of its extremely short half-life (10–15 min). This study used ultrasound (US) mediating 5-FU-loaded microbubbles (MBs) cavitation as a tool to increase local intratumoral 5-FU levels with a reduced dose of 5-FU (a single IV injection of 2.5 mg/kg instead of a single intraperitoneal injection of 25–200 mg/kg as used in previous studies in mice). The 5-FU-MBs were prepared with a 132 mg/mL albumin solution and a 0.30 mg/mL 5-FU solution. The diameters of the MBs and 5-FU-MBs were 1.24 ± 0.85 and 2.00 ± 0.53 µm (mean ± SEM), respectively, and the maximum loading efficiency of 5-FU on MBs was 19.04 ± 0.25%. In the in vitro study, the cell viabilities of 5-FU and 5-FU-MBs did not differ significantly, but compared with the 5-FU-MBs treatment-alone group, cell toxicity increased to 31% in the 5-FU-MBs + US group (p < 0.001). The biodistribution results indicated that the 5-FU levels of the tumors in small animals were significant higher for the 5-FU-MBs + US treatment than for either the 5-FU-MBs or 5-FU treatment with low 5-FU systemic treatment doses (2.5 mg/kg 5-FU IV). In small-animal treatment, 2.5 mg/kg 5-FU therapeutic IV doses injected into mice caused a more-significant reduction in tumor growth in the 5-FU-MBs + US group (65.9%) than in the control group after 34 days of treatment.https://www.tandfonline.com/doi/10.1080/10717544.2022.2154410Microbubblesultrasoundhalf-life5-fluorouracilhead nd neck cancercavitation
spellingShingle Ai-Ho Liao
Yu-An Lee
Dao-Lung Lin
Ho-Chiao Chuang
Jehng-Kang Wang
Ching-En Chang
Hsiang-Tzu Li
Ting-Yi Wu
Cheng-Ping Shih
Chih-Hung Wang
Yueng-Hsiang Chu
Treatment efficacy of low-dose 5-fluorouracil with ultrasound in mediating 5-fluorouracil-loaded microbubble cavitation in head and neck cancer
Drug Delivery
Microbubbles
ultrasound
half-life
5-fluorouracil
head nd neck cancer
cavitation
title Treatment efficacy of low-dose 5-fluorouracil with ultrasound in mediating 5-fluorouracil-loaded microbubble cavitation in head and neck cancer
title_full Treatment efficacy of low-dose 5-fluorouracil with ultrasound in mediating 5-fluorouracil-loaded microbubble cavitation in head and neck cancer
title_fullStr Treatment efficacy of low-dose 5-fluorouracil with ultrasound in mediating 5-fluorouracil-loaded microbubble cavitation in head and neck cancer
title_full_unstemmed Treatment efficacy of low-dose 5-fluorouracil with ultrasound in mediating 5-fluorouracil-loaded microbubble cavitation in head and neck cancer
title_short Treatment efficacy of low-dose 5-fluorouracil with ultrasound in mediating 5-fluorouracil-loaded microbubble cavitation in head and neck cancer
title_sort treatment efficacy of low dose 5 fluorouracil with ultrasound in mediating 5 fluorouracil loaded microbubble cavitation in head and neck cancer
topic Microbubbles
ultrasound
half-life
5-fluorouracil
head nd neck cancer
cavitation
url https://www.tandfonline.com/doi/10.1080/10717544.2022.2154410
work_keys_str_mv AT aiholiao treatmentefficacyoflowdose5fluorouracilwithultrasoundinmediating5fluorouracilloadedmicrobubblecavitationinheadandneckcancer
AT yuanlee treatmentefficacyoflowdose5fluorouracilwithultrasoundinmediating5fluorouracilloadedmicrobubblecavitationinheadandneckcancer
AT daolunglin treatmentefficacyoflowdose5fluorouracilwithultrasoundinmediating5fluorouracilloadedmicrobubblecavitationinheadandneckcancer
AT hochiaochuang treatmentefficacyoflowdose5fluorouracilwithultrasoundinmediating5fluorouracilloadedmicrobubblecavitationinheadandneckcancer
AT jehngkangwang treatmentefficacyoflowdose5fluorouracilwithultrasoundinmediating5fluorouracilloadedmicrobubblecavitationinheadandneckcancer
AT chingenchang treatmentefficacyoflowdose5fluorouracilwithultrasoundinmediating5fluorouracilloadedmicrobubblecavitationinheadandneckcancer
AT hsiangtzuli treatmentefficacyoflowdose5fluorouracilwithultrasoundinmediating5fluorouracilloadedmicrobubblecavitationinheadandneckcancer
AT tingyiwu treatmentefficacyoflowdose5fluorouracilwithultrasoundinmediating5fluorouracilloadedmicrobubblecavitationinheadandneckcancer
AT chengpingshih treatmentefficacyoflowdose5fluorouracilwithultrasoundinmediating5fluorouracilloadedmicrobubblecavitationinheadandneckcancer
AT chihhungwang treatmentefficacyoflowdose5fluorouracilwithultrasoundinmediating5fluorouracilloadedmicrobubblecavitationinheadandneckcancer
AT yuenghsiangchu treatmentefficacyoflowdose5fluorouracilwithultrasoundinmediating5fluorouracilloadedmicrobubblecavitationinheadandneckcancer