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INTRANASAL MICROPARTICLE DELIVERY ENHANCES BRAIN CREATINE UPTAKE ACROSS REGIONS IN MICE

Abstract

Creatine supplementation in mice enhances brain energy metabolism through increased ATP production. This study compares creatine concentrations obtained from commercially available creatine monohydrate and microparticle-based delivery systems. The mice were treated with phosphate-buffered saline (PBS), commercially available creatine monohydrate (13 mg/mL), microparticle creatine at 13 mg/mL, or microparticle creatine at 32.5 mg/mL. These treatments were administered intranasally to partially bypass the blood-brain barrier and provide direct transport to the brain. Using a colorimetric creatine assay kit, the olfactory bulb, cerebellum, and hippocampus were analyzed. The standard curve of absorbance values helped determine the creatine concentration in each respective brain region. The final creatine concentrations were adjusted for dilution, and tissue water content (0.8 mL/g) was taken into account. Brain creatine levels were lowest in the PBS-treated mice and gradually increased in both the commercially available creatine monohydrate and the microparticle creatine at 13 mg/mL. The microparticle-based delivery at 32.5 mg/mL resulted in the highest creatine concentrations. This enhancement in creatine concentration was observed across all three brain regions that were analyzed. There were regional differences in creatine elevation, with the hippocampus having a meaningful impact. The hippocampus is responsible for memory formation and spatial navigation, suggesting that creatine availability may have an impact on cognitive processes. The olfactory bulb also showed increased creatine, but this can be attributed to its proximity to the blood-brain barrier. These findings suggest that microparticle-based creatine delivery could improve brain energy metabolism in mice.