Fatemeh Roudini, Iraj Kohsari, Mahdiyeh Derakhshan, Samad Nazemi, Hassan Azhdari-Zarmehri, Mohammad Mohammad-Zadeh
Pentylenetetrazole (PTZ)-induced kindling is an established model for investigating seizure mechanisms and evaluating the efficacy of antiepileptic drugs. Novel drug delivery systems, such as nanoparticles, offer improved therapeutic outcomes by enhancing brain bioavailability and reducing adverse effects. This study investigated the effects of chitosan-encapsulated carbamazepine nanoparticles on seizure activity in PTZ-kindled mice compared with the free form of the drug. Male BALB/c mice were divided into three groups: PTZ-kindled control, PTZ + free carbamazepine, and PTZ + chitosan-encapsulated carbamazepine. Seizure stage, Stage latencies 1 and 4, seizure duration, and mortality were assessed using a modified Racine scale. The results showed that while free carbamazepine temporarily reduced seizure stage, its effect diminished over time. In contrast, the chitosan-encapsulated formulation significantly reduced seizure stage, seizure duration, prolonged latencies, and completely prevented seizure-induced mortality. Characterization of the optimized nanoparticles revealed a mean particle size of 65 nm, a polydispersity index (PDI) of 0.21, a zeta potential of -34.5 mV, and an entrapment efficiency of 55.35 %, indicating favorable stability and delivery properties. Overall, this study demonstrates that chitosan‑based nanoencapsulation of carbamazepine enhances its antiepileptic efficacy in a PTZ‑kindling model, suggesting its promise as a potential therapeutic strategy for epilepsy.