Brain Delivery of Cisplatin Using Microbubbles in Combination with Ultrasound as an Effective Therapy for Glioblastoma
Glioblastoma is a highly invasive and fatal disease. Temozolomide, a blood–brain barrier (BBB)-penetrant therapeutic agent currently used for glioblastoma, does not exhibit sufficient therapeutic effect. Cisplatin (CDDP), a versatile anticancer drug, is not considered a therapeutic option for gliobl...
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| Format: | Article |
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MDPI AG
2023-11-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/11/1599 |
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| author | Fumiko Hagiwara Daiki Omata Lisa Munakata Saori Kageyama Kazuo Maruyama Nobuki Kudo Ryo Suzuki |
| author_facet | Fumiko Hagiwara Daiki Omata Lisa Munakata Saori Kageyama Kazuo Maruyama Nobuki Kudo Ryo Suzuki |
| author_sort | Fumiko Hagiwara |
| collection | DOAJ |
| description | Glioblastoma is a highly invasive and fatal disease. Temozolomide, a blood–brain barrier (BBB)-penetrant therapeutic agent currently used for glioblastoma, does not exhibit sufficient therapeutic effect. Cisplatin (CDDP), a versatile anticancer drug, is not considered a therapeutic option for glioblastoma due to its low BBB permeability. We previously investigated the utility of microbubbles (MBs) in combination with ultrasound (US) in promoting BBB permeability and reported the efficacy of drug delivery to the brain using a minimally invasive approach. This study aimed to evaluate the feasibility of CDDP delivery to the brain using the combination of MBs and US for the treatment of glioblastoma. We used mice that were implanted with glioma-261 GFP-Luc cells expressing luciferase as the glioblastoma model. In this model, after tumor inoculation, the BBB opening was induced using MBs and US, and CDDP was simultaneously administered. We found that the CDDP concentrations were higher at the glioblastoma site where the US was applied, although CDDP normally cannot pass through the BBB. Furthermore, the survival was longer in mice treated with CDDP delivered via MBs and US than in those treated with CDDP alone or those that were left untreated. These results suggest that the combination of MBs and US is an effective antitumor drug delivery system based on BBB opening in glioblastoma therapy. |
| first_indexed | 2024-03-09T16:32:40Z |
| format | Article |
| id | doaj.art-c65ceb1e7dc246b4bbe5fb81aac8b045 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T16:32:40Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-c65ceb1e7dc246b4bbe5fb81aac8b0452023-11-24T15:00:28ZengMDPI AGPharmaceuticals1424-82472023-11-011611159910.3390/ph16111599Brain Delivery of Cisplatin Using Microbubbles in Combination with Ultrasound as an Effective Therapy for GlioblastomaFumiko Hagiwara0Daiki Omata1Lisa Munakata2Saori Kageyama3Kazuo Maruyama4Nobuki Kudo5Ryo Suzuki6Laboratory of Drug and Gene Delivery Research, Faculty of Pharma-Science, Teikyo University, Tokyo 173-8605, JapanLaboratory of Drug and Gene Delivery Research, Faculty of Pharma-Science, Teikyo University, Tokyo 173-8605, JapanLaboratory of Drug and Gene Delivery Research, Faculty of Pharma-Science, Teikyo University, Tokyo 173-8605, JapanLaboratory of Theranostics, Faculty of Pharma-Science, Teikyo University, Tokyo 173-8605, JapanLaboratory of Theranostics, Faculty of Pharma-Science, Teikyo University, Tokyo 173-8605, JapanLaboratory of Biomedical Engineering, Faculty of Information Science and Technology, Hokkaido University, Sapporo 060-0814, JapanLaboratory of Drug and Gene Delivery Research, Faculty of Pharma-Science, Teikyo University, Tokyo 173-8605, JapanGlioblastoma is a highly invasive and fatal disease. Temozolomide, a blood–brain barrier (BBB)-penetrant therapeutic agent currently used for glioblastoma, does not exhibit sufficient therapeutic effect. Cisplatin (CDDP), a versatile anticancer drug, is not considered a therapeutic option for glioblastoma due to its low BBB permeability. We previously investigated the utility of microbubbles (MBs) in combination with ultrasound (US) in promoting BBB permeability and reported the efficacy of drug delivery to the brain using a minimally invasive approach. This study aimed to evaluate the feasibility of CDDP delivery to the brain using the combination of MBs and US for the treatment of glioblastoma. We used mice that were implanted with glioma-261 GFP-Luc cells expressing luciferase as the glioblastoma model. In this model, after tumor inoculation, the BBB opening was induced using MBs and US, and CDDP was simultaneously administered. We found that the CDDP concentrations were higher at the glioblastoma site where the US was applied, although CDDP normally cannot pass through the BBB. Furthermore, the survival was longer in mice treated with CDDP delivered via MBs and US than in those treated with CDDP alone or those that were left untreated. These results suggest that the combination of MBs and US is an effective antitumor drug delivery system based on BBB opening in glioblastoma therapy.https://www.mdpi.com/1424-8247/16/11/1599blood–brain barriermicrobubbleultrasounddrug delivery systemcisplatinglioblastoma |
| spellingShingle | Fumiko Hagiwara Daiki Omata Lisa Munakata Saori Kageyama Kazuo Maruyama Nobuki Kudo Ryo Suzuki Brain Delivery of Cisplatin Using Microbubbles in Combination with Ultrasound as an Effective Therapy for Glioblastoma Pharmaceuticals blood–brain barrier microbubble ultrasound drug delivery system cisplatin glioblastoma |
| title | Brain Delivery of Cisplatin Using Microbubbles in Combination with Ultrasound as an Effective Therapy for Glioblastoma |
| title_full | Brain Delivery of Cisplatin Using Microbubbles in Combination with Ultrasound as an Effective Therapy for Glioblastoma |
| title_fullStr | Brain Delivery of Cisplatin Using Microbubbles in Combination with Ultrasound as an Effective Therapy for Glioblastoma |
| title_full_unstemmed | Brain Delivery of Cisplatin Using Microbubbles in Combination with Ultrasound as an Effective Therapy for Glioblastoma |
| title_short | Brain Delivery of Cisplatin Using Microbubbles in Combination with Ultrasound as an Effective Therapy for Glioblastoma |
| title_sort | brain delivery of cisplatin using microbubbles in combination with ultrasound as an effective therapy for glioblastoma |
| topic | blood–brain barrier microbubble ultrasound drug delivery system cisplatin glioblastoma |
| url | https://www.mdpi.com/1424-8247/16/11/1599 |
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