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Nose to brain delivery of naringin loaded transniosomes for epilepsy: formulation, characterisation, blood-brain distribution and invivo pharmacodynamic evaluation.
Journal of Liposome Research 2023 May 23
The current work limns the preparation of naringin-loaded transnioosomes (NRN-TN) to enhance NRN solubility, permeation and bioavailability via nasal mucosa for intranasal delivery. NRN-TN was created by the thin-film hydration technique, and with the BBD (Box-Behnken design), optimisation was carried out. NRN-TNopt was characterised for the vesicle size, PDI (Polydispersity index), zeta potential, entrapment efficiency (EE) and in vitro NRN release. For further assessment, nasal permeation study, study of Blood-brain distribution, TEM (Transmission Electron Microscopy), and CLSM (Confocal Scanning Laser Microscopy) were conducted withal. The NRN-TNopt exhibited spherical as well as sealed vesicles with a considerable small size of 151.3 nm, an EE of 75.23 percent, a PDI of 0.1257, and an in vitro release of 83.32 percent. CLSM investigation revealed that the new formulation allows for higher NRN permeation across nasal mucosa than the NRN solution. The blood-brain distribution investigation revealed that intranasally administered NRN-TN had a greater Cmax and AUC0-24 h than orally administered NRN-TN. Seizure activity and neuromuscular coordination as measured by the rotarod test, biochemical estimate of oxidative stress indicators, and histological investigations demonstrated that the NRN-TN has superior anti-epileptic potential in comparison to the standard diazepam. In addition, nasal toxicity studies demonstrate that the NRN-TN formulation is safer for intranasal administration. This study confirmed that the created TN vesicle formulation is a valuable carrier for the intranasal administration of NRN for the treatment of epilepsy.
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