uced by 50 times lesser than the clinically applied parenteral dose for acute epileptic seizures [48,49].Figure ten. The schematic diagram showing direct nose to brain delivery of phenytoin Caspase 6 site sodium NLCs by way of olfactory epithelium by the extracellular perineural transport mechanism.Pharmaceutics 2021, 13,20 of3.eight. In Vivo Nasal Toxicity Study The local toxic impact in the optimized NLC formulation, i.e., 50 nm sized phenytoin sodium NLC, was evaluated on each olfactory mucosa and olfactory bulb of Wistar rats and was compared with that on the manage drug resolution (drug in PBS pH 6.8) treated groups. The results are illustrated in Figure 11. Sections of 50 nm sized phenytoin sodium NLC group showing fragments lined by olfactory epithelium overlying submucosa with Bowman glands and lymphocytes and plasma cells are observed. Sections from the olfactory bulb showed regular morphology with outer nerve fibre layers, followed by glomerular layer, external plexiform layer, internal granular layer and central medulla, which was very equivalent with that with the PBS treated groups. The outcomes of the nasal histopathological studies indicated that there is no toxic effect around the microscopic structure of olfactory mucosa and olfactory bulb, because the surface epithelium lining plus the granular cellular structure in the nasal mucosa and olfactory bulb had been located fully intact [50].Figure 11. Histopathology pictures of rat’s nasal olfactory mucosa and olfactory bulb immediately after treatment with 50 nm sized phenytoin sodium NLC as well as handle drug option.4. Conclusions Within this work, we ready and characterized the biocompatible Phenytoin sodium loaded NLCs of three distinct sizes (50 nm, 5000 nm and one hundred nm) by melt emulsification approach. The in vitro drug release profile indicated a full drug release inside 15 min for 50 nm sized NLCs when compared with other sized NLCs. This instant drug release is COX-2 MedChemExpress highly necessary for the acute remedy of epilepsy. Further ex vivo permeation research demonstrated higher permeation of drugs by means of nasal olfactory epithelium from 50 nm sized phenytoin sodium NLC with enhanced flux worth when compared with other NLCs at the same time as the manage drug remedy. This higher drug permeation of NLC through olfactory epithelium resulting from its compact size as well as the lipidic nature is advantageous, whereby it reachesPharmaceutics 2021, 13,21 ofthe brain swiftly and releases the drug inside 15 min so as to generate a speedy onset of action. Moreover, in vivo pharmacokinetic research performed working with Wistar rats showed higher drug accumulation within the CSF and brain tissues in comparison with other organs inside five min for the 50 nm phenytoin sodium NLC administered through an intranasal olfactory route, which was deemed to become a safer route. However, IV phenytoin sodium marketed formulation showed higher accumulation of phenytoin sodium in the liver, indicating hepatic toxicity of drugs via IV route. Therefore, it was concluded that 50 nm sized phenytoin sodium loaded NLCs could possibly be an effective carrier for the delivery of phenytoin sodium to treat acute epileptic seizures by means of the intranasal route even though minimizing peripheral toxicity. Although enhanced olfactory uptake of 50 nm size nano lipid carriers has been demonstrated within this study, additional in vivo animal research are vital to prove the antiepileptic potential from the developed phenytoin sodium NLCs.Author Contributions: S.C.N.: conceptualization, methodology, application, validation, formal analysis, sources,
