OPTIMIZING LEVETIRACETAM SURFACTANT-BASED NANOVESICLES (LEV-NVS) GEL FOR TREATING EPILEPSY USING EXPERIMENTAL DESIGN
Keywords:intranasal, Levetiracetam, nanovesicles, brain-targeted, antiepileptic, solvent evaporation technique
Objective: To develop and estimate the intranasal delivery of Levetiracetam surfactant-based nanovesicles (Lev-Nvs) as a brain-targeted antiepileptic delivery system prepared via solvent evaporation technique.
Methods: Optimized formulation F (OPT) chosen by the Design-Expert® program gave the highest entrapment efficiency (EE%) was incorporated into the gel. An experimental design was adopted utilizing various (span 65) surfactants and different cholesterol ratios.The (Lev-Nvs) nanovesicles were formulated by solvent evaporation technique and evaluated for in-vitro characterization parameters such as zeta sizer,Transmission Electron Microscopy (TEM), zeta potential .The nasal gel was evaluated for drug-excipient interactions utilizing Fourier Transform Infrared Spectroscopy (FTIR) and subjected to in-vitro and in-vivo release studies,
Results: The results indicated that the entrapment efficiency (EE%) of Levetiracetam surfactant-based nano-vesicles (Lev-Nvs) could be modulated by the alterations in surfactant and cholesterol concentrations. Optimized formulation F (OPT) showed an entrapment efficiency of (87.9 ± 1.06 %), (206.7 ± 20.43 nm) particle size, (-34.1) zeta potential and (0.979) PDI. The nanovesicle nasal gels of the F(OPT) were prepared using Carbopol 940 at different concentrations. G 0.375 formulation showed the best in vitro drug release (87.36%) after 12 hrs. Finally, the comparative in vivo pharmaco-kinetics release studies on rats revealed considerable, sustained release of the nanovesicle nasal gel and higher relative bioavailability than an equivalent dose of oral solution (293.85%).
Conclusion: Our study proves the improved efficacy of Levetiracetam as a surfactant-based nanovesicle intranasal gel in the brain targeting antiepileptic medication.
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Copyright (c) 2022 MAHMOUD H. TEAIMA, HUSSIEN MOHAMED AHMED EL-MESSIRY, HAJAR ABDULRADI SHAKER, MOHAMED A. EL-NABARAWI, DOAA A. HELAL
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