O-BN002. Intravenous administration of poly(lactide-co-glycolide) nanoparticle encapsulating brain-derived neurotrophic factor promotes neuroprotection in an ischemic stroke model in the rat

Abstract

Introduction . Poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) are biodegradable and biocompatible drug carriers and competent at delivering neuroprotective agents to the brain following peripheral administration. Brain-derived neurotrophic factor (BDNF) could provide neuroprotection in brain insult particularly ischaemic injury. We tested the neuroprotective effect of PLGA nanoparticle-bound BDNF (NPBDNF) on a permanent middle cerebral artery occlusion (pMCAO) model of ischemic rats. Methods . Sprague-Dawley rats were divided into 4 groups of 7 rats each. Group 1 was subjected to sham operation, group 2, 3, and 4 were subjected to pMCAO. Four hours after pMCAO, group 3 and 4 were intravenously (IV) treated with BDNF and NPBDNF, respectively at 4 hours post-ischaemic induction. Functional outcome was assessed at 2 and 24 hours after pMCAO, using the modified Neurologic Severity Score (mNSS) and grid walking. Following functional assessments, rats were euthanized by terminal cardiac puncture, whereby blood was taken to assess for neurobiomarker level, the neuron spesific enolase (NSE). The brain was evaluated to measure the infarct volume. Results . The NPBDNF treated group showed significant functional improvement in mNSS, demonstrating a mild injury evidenced by a decreased in mNSS score by 2.0 and 2.1 times, respectively, when compared with pMCAO and BDNF treated groups. Grid walking test showed significant improvement by error reduction in contralateral foot slips in rats treated with NPBDNF as compared with BDNF alone by 2.00 fold. The infarct volume in rats treated with NPBDNF was significantly smaller by 1.91 fold compared to the pMCAO group and 1.95 fold compared to the BDNF treated group. These results were further corroborated by the NSE level estimates. Conclusion . NPBDNF exhibit a significant neuroprotective effect in the pMCAO model of ischemia in rats following intravenous administration during the critical period of neuroprotective window.