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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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Autores principales: Lin, En-Yi, Chen, Yu-Shuan, Li, Yuan-Sheng, Chen, Syuan-Rong, Lee, Chia-Hung, Huang, Mao-Hsuan, Chuang, Hong-Meng, Harn, Horng-Jyh, Yang, Hsueh-Hui, Lin, Shinn-Zong, Tai, Dar-Fu, Chiou, Tzyy-Wen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352271/
https://www.ncbi.nlm.nih.gov/pubmed/32575820
http://dx.doi.org/10.3390/ijms21124408
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author Lin, En-Yi
Chen, Yu-Shuan
Li, Yuan-Sheng
Chen, Syuan-Rong
Lee, Chia-Hung
Huang, Mao-Hsuan
Chuang, Hong-Meng
Harn, Horng-Jyh
Yang, Hsueh-Hui
Lin, Shinn-Zong
Tai, Dar-Fu
Chiou, Tzyy-Wen
author_facet Lin, En-Yi
Chen, Yu-Shuan
Li, Yuan-Sheng
Chen, Syuan-Rong
Lee, Chia-Hung
Huang, Mao-Hsuan
Chuang, Hong-Meng
Harn, Horng-Jyh
Yang, Hsueh-Hui
Lin, Shinn-Zong
Tai, Dar-Fu
Chiou, Tzyy-Wen
author_sort Lin, En-Yi
collection PubMed
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.
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spelling pubmed-73522712020-07-21 Liposome Consolidated with Cyclodextrin Provides Prolonged Drug Retention Resulting in Increased Drug Bioavailability in Brain Lin, En-Yi Chen, Yu-Shuan Li, Yuan-Sheng Chen, Syuan-Rong Lee, Chia-Hung Huang, Mao-Hsuan Chuang, Hong-Meng Harn, Horng-Jyh Yang, Hsueh-Hui Lin, Shinn-Zong Tai, Dar-Fu Chiou, Tzyy-Wen Int J Mol Sci Article 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. MDPI 2020-06-21 /pmc/articles/PMC7352271/ /pubmed/32575820 http://dx.doi.org/10.3390/ijms21124408 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lin, En-Yi
Chen, Yu-Shuan
Li, Yuan-Sheng
Chen, Syuan-Rong
Lee, Chia-Hung
Huang, Mao-Hsuan
Chuang, Hong-Meng
Harn, Horng-Jyh
Yang, Hsueh-Hui
Lin, Shinn-Zong
Tai, Dar-Fu
Chiou, Tzyy-Wen
Liposome Consolidated with Cyclodextrin Provides Prolonged Drug Retention Resulting in Increased Drug Bioavailability in Brain
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352271/
https://www.ncbi.nlm.nih.gov/pubmed/32575820
http://dx.doi.org/10.3390/ijms21124408
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