Duchenne muscular dystrophy (DMD) is a genetic disease in which skeletal muscle membranes lack the protein dystrophin, decreasing membrane stability and causing progressive muscle degeneration. DMD has no cure, but is commonly treated with glucocorticoids such as, prednisolone to reduce inflammatory symptoms and prolong ambulation. However, chronic use of Prednisolone yields systemic side effects, thus we aim to reduce the dose needed and preferentially target this drug to muscle tissue. To this end, we have focused on two strategies for improved prednisolone formulation: 1.) combination with thiamine (vitamin B1) to synergistically improve anti-inflammatory properties and 2.) entrapment within liposomes to allow a concentrated payload ultimately targeting muscle cells. Thiamine, in its diphosphate form, is a cofactor to enzymes in the TCA cycle and pentose-phosphate pathway. Mechanistically, thiamine supplementation should improve muscle weakness and inflammatory symptoms beyond prednisolone alone. Our approach used DMD and iHSKM cells treated with LPS to induce inflammation and rescued with prednisolone alone and in combination with thiamine. IL-6 protein expression by Western blot and mRNA expression by real-time PCR will be monitored, along with reactive oxygen species measurements in live cells. Further, we have prepared a liposomal prednisolone formulation co-entrapping fluorescent dye for understanding the uptake mechanism in these cells using fluorescence microscopy.
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Macri, Antonietta and Harris, Rebecca, "Maximizing the Efficiency of Prednisolone in Duchenne Muscular Dystrophy through reformulation" (2020). Research Days Posters Spring 2020. 48.