Triphenyl phosphonium coated nano-quercetin for oral delivery: Neuroprotective effects in attenuating age related global moderate cerebral ischemia reperfusion injury in rats

Abstract

Cerebral ischemia–reperfusion is a classic example of reactive oxygen species (ROS) mediated acute damage to brain. Post-ischemic reperfusion induced oxygen free radicals production causes damage to brain cell mitochondria. Antioxidants like quercetin (Qc) have potentials to manage oxidative stress related pathophysiology. However low oral bioavailability and poor cell membrane permeability restrict its therapeutic efficacy. To overcome these hurdles mitochondria specific delivery of Qc nanocapsules was designed to efficiently counteract cerebral ischemia–reperfusion induced cell death and neurodegeneration in young and aged rats. The orally deliverable quercetin loaded polymeric nanocapsules (N1QC) were made mitochondria specific by using triphenylphosphonium cation as one of the matrix components. N1QC demonstrated higher brain uptake and remarkable mitochondrial localization post cerebral ischemia–reperfusion. This unique controlled mitochondrial delivery of quercetin ameliorated histopathological severity by preserving mitochondrial structural and functional integrity through sequestering ROS thus modulating mitochondrial ROS mediated apoptotic cell death in young and aged rats.