ROS-removing nano-medicine for navigating inflammatory microenvironment to enhance anti-epileptic therapy
As a neurological disorder in the brain, epilepsy is not only associated with abnormal synchronized discharging of neurons, but also inseparable from non-neuronal elements in the altered microenvironment. Anti-epileptic drugs (AEDs) merely focusing on neuronal circuits frequently turn out deficient,...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383522004087 |
| _version_ | 1827992858491092992 |
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| author | Zheng Zhou Keying Li Yongchao Chu Chao Li Tongyu Zhang Peixin Liu Tao Sun Chen Jiang |
| author_facet | Zheng Zhou Keying Li Yongchao Chu Chao Li Tongyu Zhang Peixin Liu Tao Sun Chen Jiang |
| author_sort | Zheng Zhou |
| collection | DOAJ |
| description | As a neurological disorder in the brain, epilepsy is not only associated with abnormal synchronized discharging of neurons, but also inseparable from non-neuronal elements in the altered microenvironment. Anti-epileptic drugs (AEDs) merely focusing on neuronal circuits frequently turn out deficient, which is necessitating comprehensive strategies of medications to cover over-exciting neurons, activated glial cells, oxidative stress and chronic inflammation synchronously. Therefore, we would report the design of a polymeric micelle drug delivery system that was functioned with brain targeting and cerebral microenvironment modulation. In brief, reactive oxygen species (ROS)-sensitive phenylboronic ester was conjugated with poly-ethylene glycol (PEG) to form amphiphilic copolymers. Additionally, dehydroascorbic acid (DHAA), an analogue of glucose, was applied to target glucose transporter 1 (GLUT1) and facilitate micelle penetration across the blood‒brain barrier (BBB). A classic hydrophobic AED, lamotrigine (LTG), was encapsulated in the micelles via self-assembly. When administrated and transferred across the BBB, ROS-scavenging polymers were expected to integrate anti-oxidation, anti-inflammation and neuro-electric modulation into one strategy. Moreover, micelles would alter LTG distribution in vivo with improved efficacy. Overall, the combined anti-epileptic therapy might provide effective opinions on how to maximize neuroprotection during early epileptogenesis. |
| first_indexed | 2024-04-10T04:14:49Z |
| format | Article |
| id | doaj.art-4ff08862a83349ec8508bbd0cf9616fb |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-04-10T04:14:49Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-4ff08862a83349ec8508bbd0cf9616fb2023-03-12T04:21:02ZengElsevierActa Pharmaceutica Sinica B2211-38352023-03-0113312461261ROS-removing nano-medicine for navigating inflammatory microenvironment to enhance anti-epileptic therapyZheng Zhou0Keying Li1Yongchao Chu2Chao Li3Tongyu Zhang4Peixin Liu5Tao Sun6Chen Jiang7Department of Pharmaceutics, School of Pharmacy, Fudan University; Key Laboratory of Smart Drug Delivery, Ministry of Education; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai 201203, ChinaDepartment of Pharmaceutics, School of Pharmacy, Fudan University; Key Laboratory of Smart Drug Delivery, Ministry of Education; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai 201203, ChinaDepartment of Pharmaceutics, School of Pharmacy, Fudan University; Key Laboratory of Smart Drug Delivery, Ministry of Education; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai 201203, ChinaDepartment of Pharmaceutics, School of Pharmacy, Fudan University; Key Laboratory of Smart Drug Delivery, Ministry of Education; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai 201203, ChinaDepartment of Pharmaceutics, School of Pharmacy, Fudan University; Key Laboratory of Smart Drug Delivery, Ministry of Education; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai 201203, ChinaDepartment of Pharmaceutics, School of Pharmacy, Fudan University; Key Laboratory of Smart Drug Delivery, Ministry of Education; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai 201203, ChinaDepartment of Pharmaceutics, School of Pharmacy, Fudan University; Key Laboratory of Smart Drug Delivery, Ministry of Education; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai 201203, ChinaCorresponding author. Tel.: +86 021 51980079.; Department of Pharmaceutics, School of Pharmacy, Fudan University; Key Laboratory of Smart Drug Delivery, Ministry of Education; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai 201203, ChinaAs a neurological disorder in the brain, epilepsy is not only associated with abnormal synchronized discharging of neurons, but also inseparable from non-neuronal elements in the altered microenvironment. Anti-epileptic drugs (AEDs) merely focusing on neuronal circuits frequently turn out deficient, which is necessitating comprehensive strategies of medications to cover over-exciting neurons, activated glial cells, oxidative stress and chronic inflammation synchronously. Therefore, we would report the design of a polymeric micelle drug delivery system that was functioned with brain targeting and cerebral microenvironment modulation. In brief, reactive oxygen species (ROS)-sensitive phenylboronic ester was conjugated with poly-ethylene glycol (PEG) to form amphiphilic copolymers. Additionally, dehydroascorbic acid (DHAA), an analogue of glucose, was applied to target glucose transporter 1 (GLUT1) and facilitate micelle penetration across the blood‒brain barrier (BBB). A classic hydrophobic AED, lamotrigine (LTG), was encapsulated in the micelles via self-assembly. When administrated and transferred across the BBB, ROS-scavenging polymers were expected to integrate anti-oxidation, anti-inflammation and neuro-electric modulation into one strategy. Moreover, micelles would alter LTG distribution in vivo with improved efficacy. Overall, the combined anti-epileptic therapy might provide effective opinions on how to maximize neuroprotection during early epileptogenesis.http://www.sciencedirect.com/science/article/pii/S2211383522004087EpilepsyPolymeric micelleReactive oxygen speciesInflammationGliosisNeuroprotection |
| spellingShingle | Zheng Zhou Keying Li Yongchao Chu Chao Li Tongyu Zhang Peixin Liu Tao Sun Chen Jiang ROS-removing nano-medicine for navigating inflammatory microenvironment to enhance anti-epileptic therapy Acta Pharmaceutica Sinica B Epilepsy Polymeric micelle Reactive oxygen species Inflammation Gliosis Neuroprotection |
| title | ROS-removing nano-medicine for navigating inflammatory microenvironment to enhance anti-epileptic therapy |
| title_full | ROS-removing nano-medicine for navigating inflammatory microenvironment to enhance anti-epileptic therapy |
| title_fullStr | ROS-removing nano-medicine for navigating inflammatory microenvironment to enhance anti-epileptic therapy |
| title_full_unstemmed | ROS-removing nano-medicine for navigating inflammatory microenvironment to enhance anti-epileptic therapy |
| title_short | ROS-removing nano-medicine for navigating inflammatory microenvironment to enhance anti-epileptic therapy |
| title_sort | ros removing nano medicine for navigating inflammatory microenvironment to enhance anti epileptic therapy |
| topic | Epilepsy Polymeric micelle Reactive oxygen species Inflammation Gliosis Neuroprotection |
| url | http://www.sciencedirect.com/science/article/pii/S2211383522004087 |
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