A comparative brain Toxico-Pharmacokinetics study of a developed tannic acid nanoparticles in the treatment of epilepsy

Abstract

Epilepsy is the most popular neurological problem throughout the world. Tannic Acid (TA) is used with vitamin E (antioxidant) as desirable and safe in the treatment of epilepsy. We used central composite design (CCD) to optimize for the preparation of PLGA Nanoparticles (NPs) in the delivery of TA via intranasal to brain which gives results improvement of brain bioavailability. PLGA NPs was prepared through an emulsion solvent evaporation with the help of 3-factor, 4-level CCD to get a best optimized-NPs. 3-independent variables were chosen (PLGA, Vitamin E TPGS, and sonication time) for the optimization of best NPs. Coating of TA-PLGA-NPs with chitosan was done for enhanced antiepileptic efficacy and brain targeting as well as drug release followed by nasal permeation study. An optimized-NPs was optimized by the two variables (dependent and independent) based on the composition of PLGA (3.0%), Vitamin E TPGS (0.3%), and sonication time (5.0 min). The values of particle size, entrapment efficiency, PDI, and zeta potential were found 105.7 ± 11.02 nm, −22.3 ± 2.3 mV, 0.169 ± 0.002, and 69.31 ± 5.89% respectively based on selected dependent variables. Optimized-TA-PLGA-NPs were coated by the CS that gives the negative to positive ZP value followed by small increment of PS. On the basis of brain pharmacokinetics results, we found a great significantly (p < 0.001) enhancement of Cmax and area under curve (AUC)0–24 by treatment (intranasal and i.v.) of wistar rats. Finally, we found a great significant i.e. p < 0.001 results in the treatment of epilepsy models (increasing current electroshock & pentylenetetrazole-induced seizures with the administration of CS coated TA PLGA NPs due to their great mucoadhesive property. we also found a significant i.e. p < 0.001) enhancement of brain-bioavailability of TA followed by treated epilepsy rats due to the administration of CS coated TA PLGA NPs. There were no mortalities, neither variation morphologically of microstructure-of brain-as well as nasal-mucosa- tissues. We didn't observe no visual signs of inflammatory or necrosis that means no toxicological results.