Liposome Consolidated with Cyclodextrin Provides Prolonged Drug Retention Resulting in Increased Drug Bioavailability in Brain
Although butylidenephthalide (BP) is an efficient anticancer drug, its poor bioavailability renders it ineffective for treating drug-resistant brain tumors. However, this problem is overcome through the use of noninvasive delivery systems, including intranasal administration. Herein, the bioavailabi...
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| Format: | Article |
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MDPI AG
2020-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/12/4408 |
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| author | En-Yi Lin Yu-Shuan Chen Yuan-Sheng Li Syuan-Rong Chen Chia-Hung Lee Mao-Hsuan Huang Hong-Meng Chuang Horng-Jyh Harn Hsueh-Hui Yang Shinn-Zong Lin Dar-Fu Tai Tzyy-Wen Chiou |
| author_facet | En-Yi Lin Yu-Shuan Chen Yuan-Sheng Li Syuan-Rong Chen Chia-Hung Lee Mao-Hsuan Huang Hong-Meng Chuang Horng-Jyh Harn Hsueh-Hui Yang Shinn-Zong Lin Dar-Fu Tai Tzyy-Wen Chiou |
| author_sort | En-Yi Lin |
| collection | DOAJ |
| description | Although butylidenephthalide (BP) is an efficient anticancer drug, its poor bioavailability renders it ineffective for treating drug-resistant brain tumors. However, this problem is overcome through the use of noninvasive delivery systems, including intranasal administration. Herein, the bioavailability, drug stability, and encapsulation efficiency (EE, up to 95%) of BP were improved by using cyclodextrin-encapsulated BP in liposomal formulations (CDD1). The physical properties and EE of the CDD1 system were investigated via dynamic light scattering, transmission electron microscopy, UV–Vis spectroscopy, and nuclear magnetic resonance spectroscopy. The cytotoxicity was examined via MTT assay, and the cellular uptake was observed using fluorescence microscopy. The CDD1 system persisted for over 8 h in tumor cells, which was a considerable improvement in the retention of the BP-containing cyclodextrin or the BP-containing liposomes, thereby indicating a higher BP content in CDD1. Nanoscale CDD1 formulations were administered intranasally to nude mice that had been intracranially implanted with temozolomide-resistant glioblastoma multiforme cells, resulting in increased median survival time. Liquid chromatography–mass spectrometry revealed that drug biodistribution via intranasal delivery increased the accumulation of BP 10-fold compared to oral delivery methods. Therefore, BP/cyclodextrin/liposomal formulations have potential clinical applications for treating drug-resistant brain tumors. |
| first_indexed | 2024-03-10T18:59:44Z |
| format | Article |
| id | doaj.art-e54440723c654768a530b6882d29b9cf |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T18:59:44Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e54440723c654768a530b6882d29b9cf2023-11-20T04:30:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-06-012112440810.3390/ijms21124408Liposome Consolidated with Cyclodextrin Provides Prolonged Drug Retention Resulting in Increased Drug Bioavailability in BrainEn-Yi Lin0Yu-Shuan Chen1Yuan-Sheng Li2Syuan-Rong Chen3Chia-Hung Lee4Mao-Hsuan Huang5Hong-Meng Chuang6Horng-Jyh Harn7Hsueh-Hui Yang8Shinn-Zong Lin9Dar-Fu Tai10Tzyy-Wen Chiou11Department of Life Science, National Dong Hwa University, No. 1, Sec. 2, Da Hsueh Rd., Shou-Feng, Hualien 974301, TaiwanBioinnovation Center, Buddhist Tzu Chi Medical Foundation, Hualien 970, TaiwanDepartment of Life Science, National Dong Hwa University, No. 1, Sec. 2, Da Hsueh Rd., Shou-Feng, Hualien 974301, TaiwanDepartment of Life Science, National Dong Hwa University, No. 1, Sec. 2, Da Hsueh Rd., Shou-Feng, Hualien 974301, TaiwanDepartment of Life Science, National Dong Hwa University, No. 1, Sec. 2, Da Hsueh Rd., Shou-Feng, Hualien 974301, TaiwanBioinnovation Center, Buddhist Tzu Chi Medical Foundation, Hualien 970, TaiwanBioinnovation Center, Buddhist Tzu Chi Medical Foundation, Hualien 970, TaiwanBioinnovation Center, Buddhist Tzu Chi Medical Foundation, Hualien 970, TaiwanDepartment of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, TaiwanBioinnovation Center, Buddhist Tzu Chi Medical Foundation, Hualien 970, TaiwanDepartment of Chemistry, National Dong Hwa University, No. 1, Sec. 2, Da Hsueh Rd., Shou-Feng, Hualien 974301, TaiwanDepartment of Life Science, National Dong Hwa University, No. 1, Sec. 2, Da Hsueh Rd., Shou-Feng, Hualien 974301, TaiwanAlthough butylidenephthalide (BP) is an efficient anticancer drug, its poor bioavailability renders it ineffective for treating drug-resistant brain tumors. However, this problem is overcome through the use of noninvasive delivery systems, including intranasal administration. Herein, the bioavailability, drug stability, and encapsulation efficiency (EE, up to 95%) of BP were improved by using cyclodextrin-encapsulated BP in liposomal formulations (CDD1). The physical properties and EE of the CDD1 system were investigated via dynamic light scattering, transmission electron microscopy, UV–Vis spectroscopy, and nuclear magnetic resonance spectroscopy. The cytotoxicity was examined via MTT assay, and the cellular uptake was observed using fluorescence microscopy. The CDD1 system persisted for over 8 h in tumor cells, which was a considerable improvement in the retention of the BP-containing cyclodextrin or the BP-containing liposomes, thereby indicating a higher BP content in CDD1. Nanoscale CDD1 formulations were administered intranasally to nude mice that had been intracranially implanted with temozolomide-resistant glioblastoma multiforme cells, resulting in increased median survival time. Liquid chromatography–mass spectrometry revealed that drug biodistribution via intranasal delivery increased the accumulation of BP 10-fold compared to oral delivery methods. Therefore, BP/cyclodextrin/liposomal formulations have potential clinical applications for treating drug-resistant brain tumors.https://www.mdpi.com/1422-0067/21/12/4408glioblastoma multiformebutylidenephthalidecyclodextrinliposomestabilitybioavailability |
| spellingShingle | En-Yi Lin Yu-Shuan Chen Yuan-Sheng Li Syuan-Rong Chen Chia-Hung Lee Mao-Hsuan Huang Hong-Meng Chuang Horng-Jyh Harn Hsueh-Hui Yang Shinn-Zong Lin Dar-Fu Tai Tzyy-Wen Chiou Liposome Consolidated with Cyclodextrin Provides Prolonged Drug Retention Resulting in Increased Drug Bioavailability in Brain International Journal of Molecular Sciences glioblastoma multiforme butylidenephthalide cyclodextrin liposome stability bioavailability |
| title | Liposome Consolidated with Cyclodextrin Provides Prolonged Drug Retention Resulting in Increased Drug Bioavailability in Brain |
| title_full | Liposome Consolidated with Cyclodextrin Provides Prolonged Drug Retention Resulting in Increased Drug Bioavailability in Brain |
| title_fullStr | Liposome Consolidated with Cyclodextrin Provides Prolonged Drug Retention Resulting in Increased Drug Bioavailability in Brain |
| title_full_unstemmed | Liposome Consolidated with Cyclodextrin Provides Prolonged Drug Retention Resulting in Increased Drug Bioavailability in Brain |
| title_short | Liposome Consolidated with Cyclodextrin Provides Prolonged Drug Retention Resulting in Increased Drug Bioavailability in Brain |
| title_sort | liposome consolidated with cyclodextrin provides prolonged drug retention resulting in increased drug bioavailability in brain |
| topic | glioblastoma multiforme butylidenephthalide cyclodextrin liposome stability bioavailability |
| url | https://www.mdpi.com/1422-0067/21/12/4408 |
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