Preparation and Characterization of Creatine Microparticles With In Vitro Assessment and In Vivo Intranasal Delivery
Abstract
Abstract Background Creatine plays a central role in cellular energy buffering through the phosphocreatine system and is essential for brain development and function. Despite widespread use of oral creatine supplementation, increasing brain creatine remains inefficient because ingested creatine is preferentially taken up by skeletal muscle rather than the central nervous system, primarily constrained by the blood-brain barrier. Intranasal administration offers a noninvasive route that can bypass blood-brain barrier limitations and has been shown to increase brain creatine levels. However, intranasal delivery is restricted by small administration volumes and by the limited aqueous solubility of creatine, which caps the maximum deliverable concentration in solution-based formulations. In this study, creatine microparticles were designed to overcome the solubility-limited dose of creatine solutions, thereby increasing the amount of creatine delivered per unit volume of the intranasal passage. Results Creatine microparticles were assembled using a transient emulsion self-assembly approach, yielding particles with substantially reduced and uniform size compared with unprocessed creatine powder and creatine monohydrate. Using Calu-3 epithelial monolayers cultured on permeable supports as an in-vitro nasal mucosa model, we evaluated epithelial safety, barrier integrity, and creatine transport. Therapeutically relevant creatine microparticle suspensions did not affect cell viability…
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