Migraines affect an estimated 1.04 billion people worldwide annually. To address the global prevalence of migraines, new migraine treatments should be of utmost importance. To date, magnesium hydroxide [Mg(OH)2] and magnesium sulfate are two common treatments for delivering magnesium to patients with low intracellular levels, which are believed to be linked to migraines. One major downside to using Mg(OH)2 as an over-the-counter treatment for magnesium delivery is the possibility of side reactions in the acidic environment of the stomach, further affecting the pH stability necessary during uptake in the small intestine. To address these downfalls, Mg(OH)2 was synthesized with capping agents betaine and citrate [Mg(OH)2 B/C] to protect the Mg(OH)2 particles from side reactions in the acidic environment of the stomach. The addition of betaine is expected to improve particle absorption, distribution, and potential to cross the blood-brain barrier via the betaine transporter while citrate is expected to decrease particle size and reduce particle aggregation. Fourier transform infrared and ultraviolet-visible spectroscopy validated the presence of key Mg(OH)2 B/C functional groups present in Mg(OH)2 citrate and Mg(OH)2 betaine controls. Dynamic light scattering confirmed the average hydrodynamic diameter of Mg(OH)2 decreased with capping agents betaine and citrate from 960 nm to 660 nm. Likewise, the average pH of the Mg(OH)2 B/C particle solution in gastric juice over 48 hours was 7.6, slightly above neutral pH (pH ˜ 7.0-7.4) and within the pH range of the small intestine (pH ˜ 6-8). Scanning electron microscopy energy dispersive x-ray spectroscopy analyzed the atomic composition of the Mg(OH)2 B/C particle core, revealing a high density of magnesium and oxygen in the Mg(OH)2 particle core. In gastric juice, the high density of magnesium and oxygen were less affected in Mg(OH)2 B/C particles compared to uncoated Mg(OH)2, confirming the hypothesis capping agents betaine and citrate help protect the Mg(OH)2 core structure from side reactions in acidic environments. Lastly, cell viability studies on J774 human macrophage cells with Mg(OH)2 B/C particles, Mg(OH)2, milk of magnesia, Mg(OH)2 citrate, and Mg(OH)2 betaine confirmed normalized cell viability percentages for all treatments within a magnesium concentration range of 159 to 0.2 mM were above 100%. Thus, this study introduces a pH-stable magnesium delivery system that is safe to use while protecting the Mg(OH)2 core against the acidic environment of the stomach for use in migraine patients.
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Master of Science (M.S.)
College of Medicine
Burnett School of Biomedical Sciences
Length of Campus-only Access
Masters Thesis (Open Access)
Holderness, Ashton, "Evaluation of Magnesium Hydroxide Particles Coated with Betaine and Citrate as a Magnesium Delivery System for Migraine Treatment" (2022). Electronic Theses and Dissertations, 2020-. 1387.