Rational Design of Thermosensitive Hydrogel to Deliver Nanocrystals with Intranasal Administration for Brain Targeting in Parkinson’s Disease
Mitochondrial dysfunction is commonly detected in individuals suffering from Parkinson’s disease (PD), presenting within the form of excessive reactive oxygen species (ROS) generation as well as energy metabolism. Overcoming this dysfunction within brain tissues is an effective approach to treat PD,...
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American Association for the Advancement of Science
2021
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oai:doaj.org-article:fd3f12014f6d4b6eadcb8881921adbb82021-11-29T08:35:05ZRational Design of Thermosensitive Hydrogel to Deliver Nanocrystals with Intranasal Administration for Brain Targeting in Parkinson’s Disease2639-527410.34133/2021/9812523https://doaj.org/article/fd3f12014f6d4b6eadcb8881921adbb82021-01-01T00:00:00Zhttp://dx.doi.org/10.34133/2021/9812523https://doaj.org/toc/2639-5274Mitochondrial dysfunction is commonly detected in individuals suffering from Parkinson’s disease (PD), presenting within the form of excessive reactive oxygen species (ROS) generation as well as energy metabolism. Overcoming this dysfunction within brain tissues is an effective approach to treat PD, while unluckily, the blood-brain barrier (BBB) substantially impedes intracerebral drug delivery. In an effort to improve the delivery of efficacious therapeutic drugs to the brain, a drug delivery platform hydrogel (MAG-NCs@Gel) was designed by complexing magnolol (MAG)-nanocrystals (MAG-NCs) into the noninvasive thermosensitive poly(N-isopropylacrylamide) (PNIPAM) with self-gelation. The as-prepared MAG-NCs@Gel exhibited obvious improvements in drug solubility, the duration of residence with the nasal cavity, and the efficiency of brain targeting, respectively. Above all, continuous intranasal MAG-NCs@Gel delivery enabled MAG to cross the BBB and enter dopaminergic neurons, thereby effectively alleviating the symptoms of MPTP-induced PD. Taking advantage of the lower critical solution temperature (LCST) behavior of this delivery platform increases its viscoelasticity in nasal cavity, thus improving the efficiency of MAG-NCs transit across the BBB. As such, MAG-NCs@Gel represented an effective delivery platform capable of normalizing ROS and adenosine triphosphate (ATP) in the mitochondria of dopaminergic neurons, consequently reversing the mitochondrial dysfunction and enhancing the behavioral skills of PD mice without adversely affecting normal tissues.Yun TanYao LiuYujing LiuRui MaJingshan LuoHuijie HongXiaojia ChenShengpeng WangChuntai LiuYi ZhangTongkai ChenAmerican Association for the Advancement of SciencearticleScienceQENResearch, Vol 2021 (2021) |
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Science Q Yun Tan Yao Liu Yujing Liu Rui Ma Jingshan Luo Huijie Hong Xiaojia Chen Shengpeng Wang Chuntai Liu Yi Zhang Tongkai Chen Rational Design of Thermosensitive Hydrogel to Deliver Nanocrystals with Intranasal Administration for Brain Targeting in Parkinson’s Disease |
| description |
Mitochondrial dysfunction is commonly detected in individuals suffering from Parkinson’s disease (PD), presenting within the form of excessive reactive oxygen species (ROS) generation as well as energy metabolism. Overcoming this dysfunction within brain tissues is an effective approach to treat PD, while unluckily, the blood-brain barrier (BBB) substantially impedes intracerebral drug delivery. In an effort to improve the delivery of efficacious therapeutic drugs to the brain, a drug delivery platform hydrogel (MAG-NCs@Gel) was designed by complexing magnolol (MAG)-nanocrystals (MAG-NCs) into the noninvasive thermosensitive poly(N-isopropylacrylamide) (PNIPAM) with self-gelation. The as-prepared MAG-NCs@Gel exhibited obvious improvements in drug solubility, the duration of residence with the nasal cavity, and the efficiency of brain targeting, respectively. Above all, continuous intranasal MAG-NCs@Gel delivery enabled MAG to cross the BBB and enter dopaminergic neurons, thereby effectively alleviating the symptoms of MPTP-induced PD. Taking advantage of the lower critical solution temperature (LCST) behavior of this delivery platform increases its viscoelasticity in nasal cavity, thus improving the efficiency of MAG-NCs transit across the BBB. As such, MAG-NCs@Gel represented an effective delivery platform capable of normalizing ROS and adenosine triphosphate (ATP) in the mitochondria of dopaminergic neurons, consequently reversing the mitochondrial dysfunction and enhancing the behavioral skills of PD mice without adversely affecting normal tissues. |
| format |
article |
| author |
Yun Tan Yao Liu Yujing Liu Rui Ma Jingshan Luo Huijie Hong Xiaojia Chen Shengpeng Wang Chuntai Liu Yi Zhang Tongkai Chen |
| author_facet |
Yun Tan Yao Liu Yujing Liu Rui Ma Jingshan Luo Huijie Hong Xiaojia Chen Shengpeng Wang Chuntai Liu Yi Zhang Tongkai Chen |
| author_sort |
Yun Tan |
| title |
Rational Design of Thermosensitive Hydrogel to Deliver Nanocrystals with Intranasal Administration for Brain Targeting in Parkinson’s Disease |
| title_short |
Rational Design of Thermosensitive Hydrogel to Deliver Nanocrystals with Intranasal Administration for Brain Targeting in Parkinson’s Disease |
| title_full |
Rational Design of Thermosensitive Hydrogel to Deliver Nanocrystals with Intranasal Administration for Brain Targeting in Parkinson’s Disease |
| title_fullStr |
Rational Design of Thermosensitive Hydrogel to Deliver Nanocrystals with Intranasal Administration for Brain Targeting in Parkinson’s Disease |
| title_full_unstemmed |
Rational Design of Thermosensitive Hydrogel to Deliver Nanocrystals with Intranasal Administration for Brain Targeting in Parkinson’s Disease |
| title_sort |
rational design of thermosensitive hydrogel to deliver nanocrystals with intranasal administration for brain targeting in parkinson’s disease |
| publisher |
American Association for the Advancement of Science |
| publishDate |
2021 |
| url |
https://doaj.org/article/fd3f12014f6d4b6eadcb8881921adbb8 |
| work_keys_str_mv |
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| _version_ |
1718407503126986752 |