Lipid nanoparticles (LNPs), utilized in the Pfizer and Moderna COVID-19 vaccine formulations, are necessary to safely and effectively deliver mRNA intracellularly. Optimization of nanoparticle formulations remains crucial to improve the effectiveness of mRNA delivery. We hypothesised that glycogen nanoparticles, being an abundant and naturally occurring molecule within the body, would be better than standard LNPs in terms of biocompatibility, and that metabolite-containing LNPs would have greater transfection efficiency as energy carriers. Particles were formed using microfluidic mixing and characterized using dynamic light scattering (DLS) and atomic force microscopy (AFM), which determined the size, surface charge, and 3D structure of the particles. Candidate nanoparticles were then introduced to Huh-7 cells before microplate reader measurements and fluorescent microscopy were used to assess expression of fluorescent reporter genes. Transfection efficiency was investigated with in vitro flow cytometry. Transfection of mRNA with glycogen LNPs was ineffective compared to a gold-standard LNP formulation (Pfizer) in both plate reader and microscopy assays. Lipid nanoparticles with adenosine triphosphate (ATP) showed effective transfection but were not superior to the Pfizer LNP formulation in plate reader measurements, microscopy or flow cytometry. Our results indicate that glycogen, with an overall negative charge, may need further modulation of surface charge to ensure stability and prevent aggregation of the nanoparticles. LNPs with ATP should be compared to more metabolite formulations to better understand the effects of ATP on the delivery system. Overall, these findings investigated fundamental aspects of mRNA delivery, which has applications in the development of novel vaccines and gene therapies.