Abstract
Magnesium (Mg2+) is the fourth most abundant cation in the human body and is involved in maintaining varieties of cellular and neurological functions. Magnesium deficiency has been associated with numerous diseases, particularly neurological disorders, and its supplementation has proven beneficial. However, magnesium therapy in neurological diseases is limited because of the inability of magnesium to cross the blood–brain barrier (BBB). The present study focuses on developing magnesium sulphate nanoparticles (MGSN) to improve blood–brain barrier permeability. MGSN was prepared by precipitation technique with probe sonication. The developed formulation was characterized by DLS, EDAX, FT-IR and quantitative and qualitative estimation of magnesium. According to the DLS report, the average size of the prepared MGSN is found to be 247 nm. The haemocompatibility assay studies revealed that the prepared MGSN are biocompatible at different concentrations. The in vitro BBB permeability assay conducted by Parallel Artificial Membrane Permeability Assay (PAMPA) using rat brain tissue revealed that the prepared MGSN exhibited enhanced BBB permeability as compared to the marketed i.v. MgSO4 injection. The reversal effect of MGSN to digoxin-induced Na+/K+ ATPase enzyme inhibition using brain microslices confirmed that MGSN could attenuate the altered levels of Na+ and K+ and is useful in treating neurological diseases with altered expression of Na+/K+ ATPase activity.
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Acknowledgements
The authors are grateful to the ‘Amrita School of Pharmacy, Kochi, Kerala’ for providing all the infrastructure facilities to conduct the work as well as Dr. S K Kanthlal for the support and guidance in conducting the in vitro studies.
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A seed grant fund supported this work from Amrita Vishwa Vidyapeetham with Seed Grant Number: K-PHAR-20–629.
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All the authors contributed to the study’s conception and design. SM and AAM performed the material preparation, data collection and analysis. The first draft of the manuscript was written by SM and AAM, and all the authors commented on previous versions. Supervision of the work and critical review of the article were done by RP. All the authors read and approved the final manuscript.
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All experiments were carried out with the consent of the Amrita Vishwa Vidyapeetham Animal Care and Ethics Committee and in compliance with CPCSEA rules and regulations and the IAEC Code of Practice for the Care and Use of Animals for Scientific Purposes (Ref.no: IAEC/2019/3/6 Amend).
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Mathew, A.A., Mohapatra, S. & Panonnummal, R. Formulation and evaluation of magnesium sulphate nanoparticles for improved CNS penetrability. Naunyn-Schmiedeberg's Arch Pharmacol 396, 567–576 (2023). https://doi.org/10.1007/s00210-022-02356-7
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DOI: https://doi.org/10.1007/s00210-022-02356-7