No abstract

Nanocrystals are used as universal approach to improve the bioactivity of poorly soluble active ingredients. They are produced by various techniques, typically yielding aqueous nanosuspensions, which are prone to microbial contamination. Preservation of nanocrystals is possible but might not always be feasible, as preservatives might interfere with other excipients in the formulations or with chemicals used in assays, cell cultures or animal models. Therefore, to enable an easier use of nanocrystals, preservative-free nanosuspensions would be a good alternative. In this study, rutin nanocrystals were frozen and stored for three months at −20 °C. The chemical, physical and microbial stability were monitored, and the results were compared to preserved nanosuspensions. The frozen nanosuspensions remained stable and possessed excellent stability over the whole time of storage, indicating that the freeze–thaw process is suitable for the production of preservative-free nanosuspensions with excellent long-term stability. The freeze–thaw process for nanosuspensions is a simple concept and is suggested as alternative, when preserved nanosuspensions cannot be used.

Motoric disturbances in Parkinson’s disease (PD) derive from the loss of dopaminergic neurons in the substantia nigra. Intestinal dysfunctions often appear long before manifestation of neuronal symptoms, suggesting a strong correlation between gut and brain in PD. Oxidative stress is a key player in neurodegeneration causing neuronal cell death. Using natural antioxidative flavonoids like Rutin, might provide intervening strategies to improve PD pathogenesis. To explore the potential effects of micro (mRutin) compared to nano Rutin (nRutin) upon the brain and the gut during PD, its neuroprotective effects were assessed using an in vitro PD model. Our results demonstrated that Rutin inhibited the neurotoxicity induced by A53T α-synuclein (Syn) administration by decreasing oxidized lipids and increasing cell viability in both, mesencephalic and enteric cells. For enteric cells, neurite outgrowth, number of synaptic vesicles, and tyrosine hydroxylase positive cells were significantly reduced when treated with Syn. This could be reversed by the addition of Rutin. nRutin revealed a more pronounced result in all experiments. In conclusion, our study shows that Rutin, especially the nanocrystals, are promising natural compounds to protect neurons from cell death and oxidative stress during PD. Early intake of Rutin may provide a realizable option to prevent or slow PD pathogenesis.