Rapid and improved oral absorption of N-butylphthalide by sodium cholate-appended liposomes for efficient ischemic stroke therapy
As a multi-target drug to treat ischemic stroke, N-butylphthalide (NBP) is extremely water-insoluble and exhibits limited oral bioavailability, impeding its wide oral application. Effective treatment of ischemic stroke by NBP requires timely and efficient drug exposure, necessitating the development...
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Taylor & Francis Group
2021
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oai:doaj.org-article:90acf7aac0654f6b982a7a7cae89fb532021-11-17T14:21:55ZRapid and improved oral absorption of N-butylphthalide by sodium cholate-appended liposomes for efficient ischemic stroke therapy1071-75441521-046410.1080/10717544.2021.2000678https://doaj.org/article/90acf7aac0654f6b982a7a7cae89fb532021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/10717544.2021.2000678https://doaj.org/toc/1071-7544https://doaj.org/toc/1521-0464As a multi-target drug to treat ischemic stroke, N-butylphthalide (NBP) is extremely water-insoluble and exhibits limited oral bioavailability, impeding its wide oral application. Effective treatment of ischemic stroke by NBP requires timely and efficient drug exposure, necessitating the development of new oral formulations. Herein, liposomes containing biosurfactant sodium cholate (CA-liposomes) were systemically investigated as an oral NBP delivery platform because of its high biocompatibility and great potential for clinical applications. The optimized liposomes have a uniform hydrodynamic size of 104.30 ± 1.60 nm and excellent encapsulation efficiency (93.91 ± 1.10%). Intriguingly, NBP-loaded CA-liposomes produced rapid drug release and the cumulative release was up to 88.09 ± 4.04% during 12 h while that for NBP group was only 6.79 ± 0.99%. Caco-2 cell monolayer assay demonstrated the superior cell uptake and transport efficiency of NBP-loaded CA-liposomes than free NBP, which was mediated by passive diffusion via transcellular and paracellular routes. After oral administration to rats, NBP-loaded CA-liposomes exhibited rapid and almost complete drug absorption, with a tmax of 0.70 ± 0.14 h and an absolute bioavailability of 92.65% while NBP suspension demonstrated relatively low bioavailability (21.7%). Meanwhile, NBP-loaded CA-liposomes produced 18.30-fold drug concentration in the brain at 5 min compared with NBP suspension, and the brain bioavailability increased by 2.48-fold. As expected, NBP-loaded CA-liposomes demonstrated significant therapeutic efficacy in a middle cerebral artery occlusion rat model. Our study provides new insights for engineering oral formulations of NBP with fast and sufficient drug exposure against ischemic stroke in the clinic.Ailing ZhangJianbo LiShuaishuai WangYaru XuQinglian LiZhe WuChenxu WangHaiyang MengJinjie ZhangTaylor & Francis Grouparticleischemic strokerapid absorptionbrain accumulationdrug releasen-butylphthalideTherapeutics. PharmacologyRM1-950ENDrug Delivery, Vol 28, Iss 1, Pp 2469-2479 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
ischemic stroke rapid absorption brain accumulation drug release n-butylphthalide Therapeutics. Pharmacology RM1-950 |
| spellingShingle |
ischemic stroke rapid absorption brain accumulation drug release n-butylphthalide Therapeutics. Pharmacology RM1-950 Ailing Zhang Jianbo Li Shuaishuai Wang Yaru Xu Qinglian Li Zhe Wu Chenxu Wang Haiyang Meng Jinjie Zhang Rapid and improved oral absorption of N-butylphthalide by sodium cholate-appended liposomes for efficient ischemic stroke therapy |
| description |
As a multi-target drug to treat ischemic stroke, N-butylphthalide (NBP) is extremely water-insoluble and exhibits limited oral bioavailability, impeding its wide oral application. Effective treatment of ischemic stroke by NBP requires timely and efficient drug exposure, necessitating the development of new oral formulations. Herein, liposomes containing biosurfactant sodium cholate (CA-liposomes) were systemically investigated as an oral NBP delivery platform because of its high biocompatibility and great potential for clinical applications. The optimized liposomes have a uniform hydrodynamic size of 104.30 ± 1.60 nm and excellent encapsulation efficiency (93.91 ± 1.10%). Intriguingly, NBP-loaded CA-liposomes produced rapid drug release and the cumulative release was up to 88.09 ± 4.04% during 12 h while that for NBP group was only 6.79 ± 0.99%. Caco-2 cell monolayer assay demonstrated the superior cell uptake and transport efficiency of NBP-loaded CA-liposomes than free NBP, which was mediated by passive diffusion via transcellular and paracellular routes. After oral administration to rats, NBP-loaded CA-liposomes exhibited rapid and almost complete drug absorption, with a tmax of 0.70 ± 0.14 h and an absolute bioavailability of 92.65% while NBP suspension demonstrated relatively low bioavailability (21.7%). Meanwhile, NBP-loaded CA-liposomes produced 18.30-fold drug concentration in the brain at 5 min compared with NBP suspension, and the brain bioavailability increased by 2.48-fold. As expected, NBP-loaded CA-liposomes demonstrated significant therapeutic efficacy in a middle cerebral artery occlusion rat model. Our study provides new insights for engineering oral formulations of NBP with fast and sufficient drug exposure against ischemic stroke in the clinic. |
| format |
article |
| author |
Ailing Zhang Jianbo Li Shuaishuai Wang Yaru Xu Qinglian Li Zhe Wu Chenxu Wang Haiyang Meng Jinjie Zhang |
| author_facet |
Ailing Zhang Jianbo Li Shuaishuai Wang Yaru Xu Qinglian Li Zhe Wu Chenxu Wang Haiyang Meng Jinjie Zhang |
| author_sort |
Ailing Zhang |
| title |
Rapid and improved oral absorption of N-butylphthalide by sodium cholate-appended liposomes for efficient ischemic stroke therapy |
| title_short |
Rapid and improved oral absorption of N-butylphthalide by sodium cholate-appended liposomes for efficient ischemic stroke therapy |
| title_full |
Rapid and improved oral absorption of N-butylphthalide by sodium cholate-appended liposomes for efficient ischemic stroke therapy |
| title_fullStr |
Rapid and improved oral absorption of N-butylphthalide by sodium cholate-appended liposomes for efficient ischemic stroke therapy |
| title_full_unstemmed |
Rapid and improved oral absorption of N-butylphthalide by sodium cholate-appended liposomes for efficient ischemic stroke therapy |
| title_sort |
rapid and improved oral absorption of n-butylphthalide by sodium cholate-appended liposomes for efficient ischemic stroke therapy |
| publisher |
Taylor & Francis Group |
| publishDate |
2021 |
| url |
https://doaj.org/article/90acf7aac0654f6b982a7a7cae89fb53 |
| work_keys_str_mv |
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