Administration of resveratrol and cyclosporine a nanoparticles in a hypoxia/reoxygenation model

Ischemia reperfusion (I/R) injury remains as a neglected therapeutic target, limiting the benefits on morbidity and mortality of early reperfusion therapies. In this work, two separate poly(lactic-co-glycolic) acid (PLGA) nanoparticles incorporating resveratrol (Resv-NPs), a phytoalexin with strong antioxidant potential, and cyclosporine A (CsA-NPs), a pharmacological inhibitor of the mitochondrial permeability transition pore (mPTP), were developed. These molecules present limitations in their pharmacokinetic profiles which obstruct them from being effectively applied as a treatment for I/R injury. In a H9c2 rat cardiomyoblast model of hypoxia/reoxygenation injury, free drugs were compared with their encapsulated counterparts through the assessment of cell viability. In terms of the latter, Resv-NPs appeared to have an equivalent protection than that of free Resv, however, CsA-NPs appeared to widen CsA narrow therapeutic window under the conditions here reported. mPTP opening was assessed through a Ca2+ retention capacity (CRC) assay, where encapsulation appeared to improve Resv-induced inhibition of pore opening at a concentration of 0.1 μM, while both free and encapsulated CsA groups appeared to prevent mPTP opening. The potential in vivo applications of these nanoformulations as well as the perspectives of this work are described.