Microfluidic Synthesis of Ultrasmall Chitosan/Graphene Quantum Dots Particles for Intranasal Delivery in Alzheimer's Disease Treatment

鼻腔给药 药物输送到大脑 跨细胞 神经炎症 血脑屏障 体内 药物输送 海马结构 纳米技术 化学 活力测定 药理学 量子点 纽恩 生物物理学 材料科学 神经科学 体外 炎症 医学 免疫学 生物 中枢神经系统 生物化学 生物技术 免疫组织化学
作者
Fariba Mohebichamkhorami,Mehrdad Faizi,Matin Mahmoudifard,Arman Hajikarim‐Hamedani,Seyedeh Sarvenaz Mohseni,Amirhossein Heidari,Yekta Ghane,Mona Khoramjouy,Maryam Khayati,Rasoul Ghasemi,Hakimeh Zali,Simzar Hosseinzadeh,Ebrahim Mostafavi
出处
期刊:Small [Wiley]
卷期号:19 (40) 被引量:16
标识
DOI:10.1002/smll.202207626
摘要

Nanoparticles (NPs) based therapies for Alzheimer's disease (AD) attract interest due to their ability to pass across or bypass the blood-brain barrier. Chitosan (CS) NPs or graphene quantum dots (GQDs) are promising drug carriers with excellent physicochemical and electrical properties. The current study proposes the combination of CS and GQDs in ultrasmall NP form not as drug carriers but as theranostic agents for AD. The microfluidic-based synthesis of the CS/GQD NPs with optimized characteristics makes them ideal for transcellular transfer and brain targeting after intranasal (IN) delivery. The NPs have the ability to enter the cytoplasm of C6 glioma cells in vitro and show dose and time-dependent effects on the viability of the cells. IN administration of the NPs to streptozotocin (STZ) induced AD-like models lead to a significant number of entrances of the treated rats to the target arm in the radial arm water maze (RAWM) test. It shows the positive effect of the NPs on the memory recovery of the treated rats. The NPs are detectable in the brain via in vivo bioimaging due to GQDs as diagnostic markers. The noncytotoxic NPs localize in the myelinated axons of hippocampal neurons. They do not affect the clearance of amyloid β (Aβ) plaques at intercellular space. Moreover, they showed no positive impact on the enhancement of MAP2 and NeuN expression as markers of neural regeneration. The memory improvement in treated AD rats may be due to neuroprotection via the anti-inflammation effect and regulation of the brain tissue microenvironment that needs to be studied.
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