Abstract
In the present study we investigated the protective role of intranasal rosuvastatin liquid crystalline nanoparticles (Ros-LCNPs) against pentylenetetrazole (PTZ) induced seizures, increasing current electroshock (ICES) induced seizures, and PTZ-induced status epilepticus. From the dose titration study, it was evident that intranasal rosuvastatin (ROS), at lower dose, was more effective than oral and intraperitoneal ROS. The Ros-LCNPs equivalent to 5 mg/kg ROS were developed by hydrotrope method using glyceryl monooleate (GMO) as lipid phase. The high resolution TEM revealed that the formed Ros-LCNPs were cubic shaped and multivesicular with mean size of 219.15 ± 8.14 nm. The Ros-LCNPs showed entrapment efficiency of 70.30 ± 1.84% and release was found to be biphasic following Korsmeyer–Peppas kinetics. Intranasal Ros-LCNPs (5 mg/kg) showed significant increase in latency to PTZ-induced seizures and ICES seizure threshold compared to control and intranasal ROS solution. Additionally, intranasal Ros-LCNPs provided effective protection against PTZ-induced status epilepticus. No impairment in cognitive functions was observed following intranasal Ros-LCNPs. The results suggested that Ros-LCNPs could be an effective and promising therapeutics for the epilepsy management.
Highlights
Epilepsy is one of the most severe neurological disease affecting nearly 80 million people worldwide [1]
The present study explores the neuroprotective effect of intranasal Ros-liquid crystalline nanoparticles (LCNPs) against seizures induced by pentylenetetrazole (PTZ), increasing current electroshock (ICES), and in status epilepticus [17]
The results showed that, irrespective of route of administration, the protective effect of ROS for both myoclonic jerks (MJ) and generalized seizures (GS) was dose dependent and an increase in latency time was observed with increase in ROS dose
Summary
Epilepsy is one of the most severe neurological disease affecting nearly 80 million people worldwide [1]. The 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors (statins) are potent cholesterol-lowering drugs which could potentially be repurposed as an alternative for the management of epilepsy [2]. Early long-term statin treatment has anti-epileptogenic effects in experiments performed on WAG/Rij rats (absence epilepsy animal genetic model) [4]. Most of the published reports demonstrated the anticonvulsant effects of statins, atorvastatin, following intravenous or oral doses at high concentrations [5,6,7,8]. The present study evaluates the anti-epileptic effects of intranasal rosuvastatin (ROS). ROS is more potent HMG-CoA reductase inhibitor and HMG-CoA reductase activity is reported to be correlated with anti-epileptic effects. Intranasal route offers myriads of advantages over oral and intravenous administration including possibility of self-administration, higher patient compliance, avoidance of gastrointestinal degradation and hepatic metabolism, avoidance of blood-brain barrier, and exploitation of nose to brain (olfactory) pathway to deliver the drug directly and rapidly to the brain [10,11]
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