Targeting of Thymoquinone-loaded mesoporous silica nanoparticles to different brain areas: In vivo study

Aims: Drug delivery to the brain is hindered by the blood-brain-barrier (BBB) that filters out most of drugs after systemic administration. Therefore, there is an urgent need to develop more efficient drug delivery systems to deliver pharmaceuticals to brain. In this work, the distribution and the effect of Thymoquinone (TQ) on different oxidative stress biomarkers in different brain areas, either in the free form or encapsulated in mesoposrous silica nanocarriers (MSNs) were systematically studied. Materials and methods: MSNs and Thymoquinone-loaded mesoporous silica nanoparticles (MSN-TQ) were prepared and characterized using TEM, DLS, and zeta potential. The encapsulation efficiency and release profile of MSN-TQ were investigated as well. The chromatographic quantification of TQ was carried out to evaluate the effect of TQ loading in MSNs on the TQ distribution throughout different brain regions. Additionally, some oxidative stress biomarkers were evaluated like: glutathione reduced (GSH), glutathione-s-transferase (GST), nitric acid (NO) and malondialdehyde (MDA). Key findings: Results showed that the encapsulation of TQ in MSNs enhanced its delivery to some brain areas (cortex, thalamus, hypothalamus and midbrain), on the other hand it reduced its delivery to the cerebellum while its delivery to medulla and striatum was not changed compared to free TQ. Neither free TQ nor MSN-TQ were able to reach the hippocampus. Significance: It was found that the encapsulation of TQ in MSNs resulted in its redistribution in different brain areas, thus, MSNs could be potentially utilized as a drug delivery system for selectively targeting the drug to certain brain areas.