Vesicles of yeast cell wall-sitagliptin to alleviate neuroinflammation in Alzheimer's disease

A cell-based drug delivery system based on yeast-cell wall loaded with sitagliptin, a drug with an anti-inflammatory effect, was developed to control neuroinflammation associated with Alzheimer's disease. The optimized nanoparticles had a spherical shape with a negative surface charge, and were shown to be less toxic than the carrier and sitagliptin. Moreover, the nanoparticles caused anti-inflammatory effects against tumor necrosis factor-alpha in mice model of neuroinflammation. The pharmacokinetics study showed the brain concentration of drug in the nanoparticles group was much higher than in the control group. To evaluate the effect of P-glycoprotein on brain entry of sitagliptin, the experiment was repeated with verapamil, as a P-glycoprotein inhibitor. Brain concentration of the nanoparticles group remained approximately unchanged, proving the “Trojan Horse” effect of the developed nanocarriers. The results are promising for using yeast-cell wall as a carrier for targeted delivery to immune cells for the management of inflammation. The yeast-cell wall was extracted, coated with polysorbate 80, and loaded with sitagliptin to prepare the nanoparticles for targeted drug delivery to the microglia. The optimized nanoparticles had a spherical shape and released sitagliptin in a controlled manner. Cell evaluation studies indicated that the nanoparticles had lower toxicity than the carrier and sitagliptin. Moreover, the nanoparticles caused anti-inflammatory effects against TNF-alpha in mice model of neuroinflammation. The pharmacokinetics study showed the nanoparticles can cross the blood-brain barrier, and provide higher brain concentration of the drug. [Display omitted] •Yeast-cell wall can release its cargo in a controlled-manner.•Yeast-cell wall loaded with sitagliptin ameliorates inflammation.•Yeast-cell wall can cross the blood-brain barrier.•Sitagliptin retains longer time in the brain by loading at yeast-cell wall.