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. 2020 Oct 30;13(11):356.
doi: 10.3390/ph13110356.

Liquid Crystalline Nanoparticles for Nasal Delivery of Rosuvastatin: Implications on Therapeutic Efficacy in Management of Epilepsy

Mohammad Zubair Ahmed  1 , Urooj A Khan  1 , Abdul Haye  2 , Nidhi B Agarwal  3 , Nabil A Alhakamy  4 , Hani A Alhadrami  5   6 , Musarrat Husain Warsi  7 , Gaurav K Jain  8
Affiliations

Liquid Crystalline Nanoparticles for Nasal Delivery of Rosuvastatin: Implications on Therapeutic Efficacy in Management of Epilepsy

Mohammad Zubair Ahmed et al. Pharmaceuticals (Basel). .

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.

Keywords: epilepsy; intranasal delivery; liquid crystalline nanoparticles; rosuvastatin; seizures; status epilepticus.

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Conflict of interest statement

Authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Effect of oral, i.p. and nasal route of administration of intranasal rosuvastatin (ROS) on mean latency to pentylenetetrazole (PTZ)-induced seizures; p > 0.5, nasal 5 mg/kg vs. nasal 10 mg/kg; p < 0.001, control nasal vs. nasal ROS 5 mg/kg; p < 0.001 control i.p. vs. i.p. ROS 25 mg/kg.
Figure 2
Figure 2
Optimized Ros-LCNPs (A) mean particle size, 219.10 nm; polydispersity index (PDI), 0.214; (B) zeta potential, −26.2 mv with 100% peak area.
Figure 3
Figure 3
HR-TEM micrograph of Ros-LCNPs.
Figure 4
Figure 4
Release profile of Ros-LCNPs compared with ROS suspension (Ros-Susp).
See this image and copyright information in PMC

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