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

Author:

Mohebichamkhorami Fariba1,Faizi Mehrdad2,Mahmoudifard Matin3,Hajikarim‐Hamedani Arman4,Mohseni Seyedeh Sarvenaz2,Heidari Amirhossein4,Ghane Yekta5,Khoramjouy Mona6,Khayati Maryam78,Ghasemi Rasoul9,Zali Hakimeh110,Hosseinzadeh Simzar10,Mostafavi Ebrahim1112ORCID

Affiliation:

1. Department of Tissue Engineering and Applied Cell Sciences School of Advanced Technologies in Medicine Shahid Beheshti University of Medical Sciences Tehran 1968917313 Iran

2. Department of Pharmacology and Toxicology School of Pharmacy Shahid Beheshti University of Medical Sciences Tehran 19919-53381 Iran

3. Department of Industrial and Environmental Biotechnology National Institute of Genetic Engineering and Biotechnology Tehran 1497716316 Iran

4. Faculty of Medicine Tehran Medical Sciences Islamic Azad University Tehran 1916893813 Iran

5. School of Medicine Tehran University of Medical Sciences Tehran 1461884513 Iran

6. Phytochemistry Research Center Shahid Beheshti University of Medical Sciences Tehran 19919-53381 Iran

7. Department of Pharmaceutical Nanotechnology School of Pharmacy Zanjan University of Medical Sciences Zanjan 45139-56184 Iran

8. Pharmaceutical Nanotechnology Research Center Zanjan University of Medical Sciences Zanjan 45139-56184 Iran

9. Neurophysiology research center and Department of Physiology Faculty of Medicine Shahid Beheshti University of Medical Sciences Tehran 1985717443 Iran

10. Medical Nanotechnology and Tissue Engineering Research Center Shahid Beheshti University of Medical Sciences Tehran 1968917313 Iran

11. Stanford Cardiovascular Institute Stanford University School of Medicine Stanford CA 94305 USA

12. Department of Medicine Stanford University School of Medicine Stanford CA 94305 USA

Abstract

AbstractNanoparticles (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.

Funder

National Institute of Biomedical Imaging and Bioengineering

Publisher

Wiley

Subject

Biomaterials,Biotechnology,General Materials Science,General Chemistry

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