Brain-targeted intranasal pregabalin niosomes for the treatment and prevention of teratogenic congenital malformations in PTZ-induced seizures in pregnant rats without passing placental barrier.

The study evaluated the efficacy of a niosomal formulation of pregabalin (PGB) in pentylenetetrazole (PTZ)-induced seizures in pregnant rats with acute epileptic-type convulsions. The rats were divided into five groups: (1) a saline-administered negative control group of pregnant rats, (2) a positive control group receiving PTZ (3 doses on the 15th, 17th, and 19th days of pregnancy) without treatment, (3) an oral PGB group also administered PTZ 3X, (4) an intranasal PGB group with PTZ 3X, and (5) a standard-treated group receiving intraperitoneal diazepam (DIAZ plus PTZ 3X). All treatments were administered for 14 days during pregnancy. Two hours after the final PTZ injection, dams were sacrificed for fetal analysis. The objective was to determine whether niosomes could prevent placental passage of PGB while retaining its pharmacological benefits. Intranasal therapy resulted in no teratogenic effects-suggesting that PGB niosomes did not cross the placental barrier and were safe. The study also highlighted PGB's potential impact on fetal brain development, revealing abnormalities in the oral treatment group. In contrast, intranasal administration at 1250 mg/kg body weight improved seizure latency, reduced convulsion duration, and enhanced hippocampal histology without teratogenic signs. The niosomal PGB formulation effectively reduced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Bcl-2-associated X protein (BAX) expression in maternal and fetal brain tissues, potentially mitigating embryotoxicity and exhibiting antioxidant, antifibrotic, and anti-inflammatory effects. This protective action may help prevent PTZ-induced seizures, underscoring the therapeutic promise of niosomal PGB for pregnant women with acute epileptic seizures.