Development and characterisation of poly ADP-ribose polymerase inhibitor olaparib nanocarrier drug form and investigation of its effects against hydrogen peroxide-induced damage in SH-SY5Y neuroblastoma cell line

Poly (ADP-ribose) polymerases (PARP) are one of the enzymes that play a role in the repair mechanisms of damaged cells in the organism. PARP participates in the repair of DNA damage, takes part in different biological pathways in the process up to cell differentiation and apoptosis. Considering the pharmaceutical properties of Olaparib, one of the PARP inhibitors, it has been brought into nanosuspension form due to its low oil and water solubility (BCS class 4). In this study, we aimed to investigate the possible antioxidant and cytoprotective effects of Olaparib, an FDA-approved PARP inhibitor, and its nanoformulation on neuroblastomas by applying it to the oxidatively damaged human neuroblastoma cell line SH-SY5Y with hydrogen peroxide (H2O2). In our study, when the Olaparib group (OLA) and the Olaparib group (NOLA) given in nanosuspension were examined, it was seen that the NOLA 100 μM group has reduced MDA levels close to the 100 μM alpha lipoic acid group (ALA). Again, both the 100 μM OLA and NOLA groups reduced 3-NT and LDH levels similar to alpha lipoic acid. When we looked at the results we have obtained, it has been found that high-dose Olaparib administration may exhibit antioxidant and cytoprotective effects similar to alpha lipoic acid in terms of some parameters. However, these effects were not supported by all the parameters we examined. In this respect, more scientific data is needed with PARP inhibitors. The results of the study showed that nanopharmaceuticals can be promising in terms of cellular absorption and targeting for active substances such as Olaparib, which have the potential to be low in oil and water solubility.