Timed release of cerebrolysin using titanate nanospheres induces neuroprotection in Parkinson’s Disease

H.S. Sharma, D.F. Muresanu, J.V. Lafuente, A. Ozkizilcik, Z.R. Tian, R. Patnaik, H. Mössler, A. Sharma
Uppsala University,

Keywords: Parkinson's Disease, Titanate nanospheres, timed release, cerebrolysin, neuroprotection, nanodrug delivery


Military personnel during combat operations are highly susceptible to traumatic brain and spinal cord injury. There are reasons to believe that a focal injury to the central nervous system (CNS) causes multiple biochemical and pathological changes in the fluid microenvironment in which neurons and glial cells are suspended. This would lead to a process of cascade leading to neurodegenerative diseases e.g., Parkinson’s Disease (PD) and/or Alzheimer’s Diseases (AD). So far no suitable therapeutic strategies are available to reduce or contain the pathophysiology of PD/AD in clinics. Thus, there is an urgent need to explore new therapeutic strategies to reduce pathophysiological consequences of AD/PD. Since Cerebrolsyin (CBL) is a balanced composition of several neurotrophic factors and active peptide fragments, the drug could be more beneficial in treating PD. Thus, in present investigation we examined nanodelivery of CBL using titanate nanospheres in an animal model of PD and evaluated the pathophysiological responses in the brain. PD like symptoms was induced in the mice by intraperitoneal injections of or 1-metyl-4-fenyl-1,2,3,6-tetrahydropyridin (MPTP, 20 mg/kg) daily within 2-h intervals for 5 days. On the 8th day a significant decrease in dopamine (DA) and its metabolites 3,4-Dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) was observed. Marked decrease in the number of tyrosine hydroxylase (TH) positive cells in the Substantia Nigra Pars Compacta (SNpc) and striatum (STr) further confirmed the validity of our model. In separate group of rats, timed release of CBL using titanate nanospheres (TiNS) (in a dose of 3 ml/kg, i.v.) was given after 2-days of MPTP administration for 5 days. This treatment resulted in a marked increase in TH-positive cells in the SNpc and STr as compared to normal CBL. Also TiNS-CBL resulted in significantly higher levels of DA, DOPAC and HVA in SNpc and STr on the 8th day as compared to normal CBL. Tehse observations are the first to point out that timed release of TiNS-CBL has far more superior neuroprotective effects in PD than normal CBL, not reported earlier. Further research using prolonged therapeutic time window is currently being investigated in this model to find out a suitable role of TiNS-CBL in clinical situations for the benefit of PD victims in Military or civilian populations.