Polymeric Nanoparticles-Based Brain Delivery with Improved Therapeutic Efficacy of Ginkgolide B in Parkinson’s Disease
Yuying Zhao,1 Sha Xiong,1 Piaoxue Liu,1 Wei Liu,1 Qun Wang,1 Yao Liu,1 Hanxu Tan,2 Xiaojia Chen,3 Xuguang Shi,4 Qi Wang,1 Tongkai Chen1 1Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, People’s Republic of China; 2Dongzhimen Hospital, B...
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Dove Medical Press
2020
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oai:doaj.org-article:73e141f4fef54d5b893874e7b35390c72021-12-02T15:12:21ZPolymeric Nanoparticles-Based Brain Delivery with Improved Therapeutic Efficacy of Ginkgolide B in Parkinson’s Disease1178-2013https://doaj.org/article/73e141f4fef54d5b893874e7b35390c72020-12-01T00:00:00Zhttps://www.dovepress.com/polymeric-nanoparticles-based-brain-delivery-with-improved-therapeutic-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yuying Zhao,1 Sha Xiong,1 Piaoxue Liu,1 Wei Liu,1 Qun Wang,1 Yao Liu,1 Hanxu Tan,2 Xiaojia Chen,3 Xuguang Shi,4 Qi Wang,1 Tongkai Chen1 1Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, People’s Republic of China; 2Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, People’s Republic of China; 3State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, People’s Republic of China; 4School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, People’s Republic of ChinaCorrespondence: Tongkai Chen; Qi WangScience and Technology Innovation Center, Guangzhou University of Chinese Medicine, 12 Jichang Road, Guangzhou 510405, People’s Republic of ChinaEmail chentongkai@gzucm.edu.cn; wangqi@gzucm.edu.cnPurpose: Ginkgolide B (GB) is a terpene lactone derivative of Ginkgo biloba that is believed to function in a neuroprotective manner ideal for treating Parkinson’s disease (PD). Despite its promising therapeutic properties, GB has poor bioavailability following oral administration and cannot readily achieve sufficient exposure in treated patients, limiting its clinical application for the treatment of PD. In an effort to improve its efficacy, we utilized poly(ethylene glycol)-co-poly(ϵ-caprolactone) (PEG-PCL) nanoparticles as a means of encapsulating GB (GB-NPs). These NPs facilitated the sustained release of GB into the blood, thereby improving its ability to accumulate in the brain and to treat PD.Methods and Results: Using Madin-Darby canine kidney (MDCK) cells, we were able to confirm that these NPs could be taken into cells via multiple nonspecific mechanisms including micropinocytosis, clathrin-dependent endocytosis, and lipid raft/caveolae-mediated endocytosis. Once internalized, these NPs tended to accumulate in the endoplasmic reticulum and lysosomes. In zebrafish, we determined that these NPs were readily able to undergo transport across the chorion, gastrointestinal, blood–brain, and blood-retinal barriers. In a 1-methyl-4-phenylpyridinium ion (MPP+)-induced neuronal damage model system, we confirmed the neuroprotective potential of these NPs. Following oral administration to rats, GB-NPs exhibited more desirable pharmacokinetics than did free GB, achieving higher GB concentrations in both the brain and the blood. Using a murine PD model, we demonstrated that these GB-NPs achieved superior therapeutic efficacy and reduced toxicity relative to free GB.Conclusion: In conclusion, these results indicate that NPs encapsulation of GB can significantly improve its oral bioavailability, cerebral accumulation, and bioactivity via mediating its sustained release in vivo.Keywords: drug delivery system, blood–brain barrier, endocytosis, zebrafish, PD treatmentZhao YXiong SLiu PLiu WWang QLiu YTan HChen XShi XWang QChen TDove Medical Pressarticledrug delivery systemblood-brain barrierendocytosiszebrafishpd treatmentMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 10453-10467 (2020) |
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drug delivery system blood-brain barrier endocytosis zebrafish pd treatment Medicine (General) R5-920 |
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drug delivery system blood-brain barrier endocytosis zebrafish pd treatment Medicine (General) R5-920 Zhao Y Xiong S Liu P Liu W Wang Q Liu Y Tan H Chen X Shi X Wang Q Chen T Polymeric Nanoparticles-Based Brain Delivery with Improved Therapeutic Efficacy of Ginkgolide B in Parkinson’s Disease |
| description |
Yuying Zhao,1 Sha Xiong,1 Piaoxue Liu,1 Wei Liu,1 Qun Wang,1 Yao Liu,1 Hanxu Tan,2 Xiaojia Chen,3 Xuguang Shi,4 Qi Wang,1 Tongkai Chen1 1Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, People’s Republic of China; 2Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, People’s Republic of China; 3State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, People’s Republic of China; 4School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, People’s Republic of ChinaCorrespondence: Tongkai Chen; Qi WangScience and Technology Innovation Center, Guangzhou University of Chinese Medicine, 12 Jichang Road, Guangzhou 510405, People’s Republic of ChinaEmail chentongkai@gzucm.edu.cn; wangqi@gzucm.edu.cnPurpose: Ginkgolide B (GB) is a terpene lactone derivative of Ginkgo biloba that is believed to function in a neuroprotective manner ideal for treating Parkinson’s disease (PD). Despite its promising therapeutic properties, GB has poor bioavailability following oral administration and cannot readily achieve sufficient exposure in treated patients, limiting its clinical application for the treatment of PD. In an effort to improve its efficacy, we utilized poly(ethylene glycol)-co-poly(ϵ-caprolactone) (PEG-PCL) nanoparticles as a means of encapsulating GB (GB-NPs). These NPs facilitated the sustained release of GB into the blood, thereby improving its ability to accumulate in the brain and to treat PD.Methods and Results: Using Madin-Darby canine kidney (MDCK) cells, we were able to confirm that these NPs could be taken into cells via multiple nonspecific mechanisms including micropinocytosis, clathrin-dependent endocytosis, and lipid raft/caveolae-mediated endocytosis. Once internalized, these NPs tended to accumulate in the endoplasmic reticulum and lysosomes. In zebrafish, we determined that these NPs were readily able to undergo transport across the chorion, gastrointestinal, blood–brain, and blood-retinal barriers. In a 1-methyl-4-phenylpyridinium ion (MPP+)-induced neuronal damage model system, we confirmed the neuroprotective potential of these NPs. Following oral administration to rats, GB-NPs exhibited more desirable pharmacokinetics than did free GB, achieving higher GB concentrations in both the brain and the blood. Using a murine PD model, we demonstrated that these GB-NPs achieved superior therapeutic efficacy and reduced toxicity relative to free GB.Conclusion: In conclusion, these results indicate that NPs encapsulation of GB can significantly improve its oral bioavailability, cerebral accumulation, and bioactivity via mediating its sustained release in vivo.Keywords: drug delivery system, blood–brain barrier, endocytosis, zebrafish, PD treatment |
| format |
article |
| author |
Zhao Y Xiong S Liu P Liu W Wang Q Liu Y Tan H Chen X Shi X Wang Q Chen T |
| author_facet |
Zhao Y Xiong S Liu P Liu W Wang Q Liu Y Tan H Chen X Shi X Wang Q Chen T |
| author_sort |
Zhao Y |
| title |
Polymeric Nanoparticles-Based Brain Delivery with Improved Therapeutic Efficacy of Ginkgolide B in Parkinson’s Disease |
| title_short |
Polymeric Nanoparticles-Based Brain Delivery with Improved Therapeutic Efficacy of Ginkgolide B in Parkinson’s Disease |
| title_full |
Polymeric Nanoparticles-Based Brain Delivery with Improved Therapeutic Efficacy of Ginkgolide B in Parkinson’s Disease |
| title_fullStr |
Polymeric Nanoparticles-Based Brain Delivery with Improved Therapeutic Efficacy of Ginkgolide B in Parkinson’s Disease |
| title_full_unstemmed |
Polymeric Nanoparticles-Based Brain Delivery with Improved Therapeutic Efficacy of Ginkgolide B in Parkinson’s Disease |
| title_sort |
polymeric nanoparticles-based brain delivery with improved therapeutic efficacy of ginkgolide b in parkinson’s disease |
| publisher |
Dove Medical Press |
| publishDate |
2020 |
| url |
https://doaj.org/article/73e141f4fef54d5b893874e7b35390c7 |
| work_keys_str_mv |
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1718387638541484032 |