Title: Development of rotigotine nanoparticles and its effect on haloperidol induced Parkinsonian symptoms in rats

Subrat Kumar Bhattamisra

International Medical University, Malaysia


Dr. Subrat Kumar Bhattamisa has received his Ph.D. in Pharmacology from Banaras Hindu University, India in 2006 under fellowship obtained from Government of India. He then joined as Scientist at Torrent Research Centre, India and later shifted to academic. He joined International Medical University, Malaysia in 2014 and currently, he is involved in research areas linked to neurodegeneration and diabetes mellitus. He has published more than 40 research and review articles including patents.


Rotigotine, a non-ergot dopamine agonist (D2-D5 receptors) drug used in the treatment of idiopathic Parkinson’s disease (PD). Presently, its clinical use is very limited due to its poor oral bioavailability. Thus, this study was designed to develop chitosan nanoparticles (CS NPs) of rotigotine for intranasal route and further tested its efficacy in haloperidol-induced Parkinsonian symptoms in rats. Rotigotine loaded CS NPs were prepared using ionic gelation method with cross-linked tripolyphosphate. The efficacy of the nanoformulation was evaluated through akinesia, catalepsy and forced swimming behavioural test. Further, the brain samples were used for histopathological study and brain homogenates were used to estimate the lactate dehydrogenase (LDH) and catalase activity.  The mean particle size and zeta potential of rotigotine loaded chitosan nanoparticles was found to be 75.37 ± 3.37 nm and 25.53 ± 0.45 mV respectively. This formulation has an entrapment efficiency of 96.08 ± 0.01%. Intranasal rotigotine CS NPs showed a reversal in cataleptic behaviour compared to haloperidol positive control rats (P < 0.01). Similar changes were also observed in swim test and akinesia. Rotigotine loaded CS NPs showed significant increase in catalase activity (96.45 nmol/min/ml) as compared to positive control (71.15 nmol/min/ml) (P<0.01). Rotigotine loaded CS NPs showed a decrease in LDH activity (111.9 ± 9.05 IU/L) as compared to positive control (147.4 ± 18.8 IU/L). Histological examination showed that haloperidol induced and rotigotine treated groups did not have any significant changes in the neuronal structure of the cerebellum. The observations in this study suggest that intranasal administration of rotigotine loaded CS NPs can be a novel nose to brain approach in the treatment of Parkinson Disease (PD). 
Acknowledgment: This research project is funded by the Ministry of Science and Technology Innovation (MOSTI), Kuala Lumpur, Malaysia, grant number (02-02-09-SF0055).
Audience take away:
• Development and optimization process of a nanoparticle that is intended to nose to brain delivery in neurodegenerative condition.
• This concept is developed to deliver the CNS acting drugs those are having poor bioavailability.
• This research direction can be further explored by other researchers.