Abstract
Alzheimer’s disease is becoming a common disorder of the elderly population due to shrinkage of the brain size with age and many other neurological complications. To provide an effective treatment option, memantine-encapsulated polymeric nanoparticles were prepared in the study. The nanoparticles were prepared by using nanoprecipitation followed by homogenization and ultrasonication methods, characterized on the basis of particle size, polydispersity index, and zeta potential. Further, in vitro release profile, cytotoxicity analysis, and Giemsa staining were conducted. To observe the efficacy of nanoparticles in scopolamine-induced Alzheimer models in vivo studies were also carried out. The results showed that nanoparticles were in the nano range with a particle size of 58.04 nm and − 23 mV zeta potential. The in vitro release was also sustained till 24 h with ~ 100% release in selected media phosphate buffer saline, simulated nasal fluid, and artificial cerebrospinal fluid. The cytotoxicity results with ~ 98 to 100% cell viability and no morphological changes through Giemsa staining indicated that nanoparticles were not leading to cell toxicity. The gamma scintigraphy studies showed higher uptake of the drug in the target site through the intranasal route and pharmacodynamic studies indicated that nanoparticles were able to inhibit the spatial memory impairment significantly as compared to the control group. The findings clearly indicated that the developed memantine nanoparticles could act as an alternative approach for the management of Alzheimer’s disease.
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Acknowledgements
We are thankful to the Jaypee Institute of Information Technology, Noida, and INMAS, DRDO, New Delhi for providing basic infrastructural support to complete this work.
Funding
The authors are thankful to the Department of Biotechnology, Ministry of Sciences, New Delhi for providing financial support to complete this study under BioCare Women Scientist Scheme (DBT Grant No. BT/PR19580/BIC/101/865/2016).
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All authors have contributed significantly in the completion of this manuscript. Following are the details about the contribution of each author:
Atinderpal Kaur—The first author performed all the experimental work for the manuscript, interpreted the data, and drafted the manuscript.
Kuldeep Nigam—The second author helped in the completion of cytotoxicity analysis and animal studies.
Amit Tyagi—The author supervised and provided his timely guidance to the first author in carrying out pharmacokinetic studies.
Shweta Dang—The corresponding author was the mentor of the project and provide her guidance and supervised all the experimental work carried out by the first author for the development of the current manuscript.
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All the animal experiments were approved by the ethical committee of Institute of Nuclear Medicine and Allied Sciences (INMAS) Institutional Animal Ethics Committee (IAEC), New Delhi, India, vide number INM/IAEC/16/10.
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Kaur, A., Nigam, K., Tyagi, A. et al. A Preliminary Pharmacodynamic Study for the Management of Alzheimer’s Disease Using Memantine-Loaded PLGA Nanoparticles. AAPS PharmSciTech 23, 298 (2022). https://doi.org/10.1208/s12249-022-02449-9
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DOI: https://doi.org/10.1208/s12249-022-02449-9