Journal
PHARMACEUTICS
Volume 11, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/pharmaceutics11090478
Keywords
nose-to-brain delivery; siRNA; cell-penetrating peptide; polymer micelle; transient middle cerebral artery occlusion; cerebral ischemia-reperfusion injury
Categories
Funding
- Japan Society for the Promotion of Science (JSPS) [17K08249]
- Nakatomi Foundation
- Takeda Science Foundation
- Grants-in-Aid for Scientific Research [17K08249] Funding Source: KAKEN
Ask authors/readers for more resources
We previously reported that siRNA delivery to the brain is improved by the nose-to-brain delivery route and by conjugation with polyethylene glycol-polycaprolactone (PEG-PCL) polymer micelles and the cell-penetrating peptide, Tat (PEG-PCL-Tat). In this study, we evaluated the nose-to-brain delivery of siRNA targeting TNF-alpha (siTNF-alpha) conjugated with PEG-PCL-Tat to investigate its therapeutic effects on a transient middle cerebral artery occlusion (t-MCAO) rat model of cerebral ischemia-reperfusion injury. Intranasal treatment was provided 30 min after infarction induced via suturing. Two hours after infarction induction, the suture was removed, and blood flow was released. At 22 h post-reperfusion, we assessed the infarcted area, TNF-alpha production, and neurological score to determine the therapeutic effects. The infarcted area was observed over a wide range in the untreated group, whereas shrinkage of the infarcted area was observed in rats subjected to intranasal administration of siTNF-alpha with PEG-PCL-Tat micelles. Moreover, TNF-alpha production and neurological score in rats treated by intranasal administration of siTNF-alpha with PEG-PCL-Tat micelles were significantly lower than those in untreated and naked siTNF-alpha-treated rats. These results indicate that nose-to-brain delivery of siTNF-alpha conjugated with PEG-PCL-Tat micelles alleviated the symptoms of cerebral ischemia-reperfusion injury.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available