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Systematic Designing and Optimization of Polymeric Nanoparticles Using Central Composite Design: A Novel Approach for Nose-to-Brain Delivery of Donepezil Hydrochloride

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Abstract

The oral administration of donepezil hydrochloride has low brain targeting efficiency especially due to the presence of the blood–brain barrier leading to poor quality of treatment. Hence, this study aimed to systematically design chitosan nanoparticles for direct nose-to-brain delivery of donepezil hydrochloride using the Quality by Design approach for better transport to the brain avoiding the blood–brain barrier. The optimized formulation showed 180.2 nm average particle size and 0.282 polydispersity index, + 16.6 mV zeta potential, more than 90% drug release, and more than 70% drug permeation in 24 h. The studies on in-vitro drug release and ex-vivo permeation showed a sustained release pattern fulfilling Korsemeyer Peppa’s model. The confocal laser scanning micrographs showed the spherical nature of nanoparticles. The intranasal administration of donepezil hydrochloride nanoparticles in Wistar rats showed approximately 2.6 times more drug than donepezil hydrochloride solution given intranasally and approximately 10 times more drug than donepezil hydrochloride solution given orally in the brain respectively after 6 h. Further, confocal micrographs using Rhodamine B (fluorescent dye) loaded nanoparticles confirmed the localization of nanoparticles in the brain post-intranasal administration. The obtained results suggested that the chitosan nanoparticles are promising drug carriers for the nose-to-brain delivery of donepezil hydrochloride for the treatment of Alzheimer’s disease.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Abbreviations

λmax :

Maximum wavelength

AChE:

Acetylcholinesterase

AD:

Alzheimer’s disease

BBB:

Blood–brain barrier

CLS:

Confocal laser scanning

CNS:

Central nervous system

CR:

Concentration ratio

CS:

Chitosan

CT:

Crosslinking time

DDW:

Double distilled water

DH:

Donepezil hydrochloride

DoE:

Design of experiment

DPL:

Drug payload

FTIR:

Fourier transform infrared spectrophotometry

GAA:

Glacial acetic acid

HPLC:

High-performance liquid chromatography

IN:

Intranasal

NPs:

Nanoparticles

PBS:

Phosphate buffer saline

PDI:

Polydispersity index

PS:

Particle size

PY:

Process yield

RSD:

Relative standard deviation

RSM:

Response surface methodology

SD:

Standard deviation

SS:

Stirring speed

STK:

Stock solution

STPP:

Sodium tripolyphosphate

UV:

Ultraviolet

ZP:

Zeta potential

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Acknowledgements

A gift sample of donepezil hydrochloride provided by Sun Pharma Pvt. Ltd., Palashbari, Sikkim, India is thankfully acknowledged. Support provided by Prof. (Dr.) Om Prakash Katare, Professor, University Institute of Pharmaceutical Sciences, Punjab University, Chandigarh in completing experimental work is kindly acknowledged.

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The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences and Technology, Maharaja Ranjit Singh Punjab Technical University, Bathinda, 151001, Punjab, India

    Yogesh Garg, Mohit Kumar, Shruti Chopra & Amit Bhatia

  2. University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India

    Gajanand Sharma & Om Prakash Katare

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  1. Yogesh Garg
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Contributions

YG and GS: Material preparation, data collection, and analysis. MK: Collecting information, methodology. SC: Collecting information. OPK and AB: Revising draft, Conceptualization, and finalizing the manuscript.

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Correspondence to Amit Bhatia.

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Ethical approval for the use of animals was granted by the Maharaja Ranjit Singh Punjab Technical University's Institutional Animal Ethics Committee (approval number MRSPTU/IAEC/2018/16) on 16/11/2018.

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Garg, Y., Kumar, M., Sharma, G. et al. Systematic Designing and Optimization of Polymeric Nanoparticles Using Central Composite Design: A Novel Approach for Nose-to-Brain Delivery of Donepezil Hydrochloride. J Clust Sci 35, 1007–1019 (2024). https://doi.org/10.1007/s10876-023-02528-2

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