Cyclodextrin nanosponges enhance the oral pharmacokinetics and antiplatelet efficacy of prasugrel hydrochloride in Wistar rats.

The present study aimed to evaluate the pharmacokinetic and pharmacodynamic performance of an optimized prasugrel hydrochloride-loaded nanosponge formulation (PSG-NS) following oral administration and to compare its systemic exposure and antiplatelet efficacy with a marketed prasugrel tablet formulation. PSG-NS was orally administered to male Wistar rats at a dose equivalent to 5 mg/kg and compared with a marketed prasugrel tablet suspension (Prasita®). Plasma concentrations were quantified using an RP-HPLC-UV method and analyzed using non-compartmental and compartmental pharmacokinetic approaches. Pharmacodynamic efficacy was evaluated using ADP-induced platelet aggregation and a ferric chloride-induced carotid artery thrombosis model. The PSG-NS formulation demonstrated significantly enhanced systemic exposure compared with Prasita®. PSG-NS achieved a significantly higher Cmax (1245.6 ± 68.3 ng/mL) with a shorter median Tmax of 0.5 h (0.5-1.0 h) compared with Prasita®, which exhibited a Cmax of 456.2 ± 31.4 ng/mL and a median Tmax of 1.0 h (0.5-2.0 h) (p < 0.001). The AUC0-∞ increased from 3412.7 ± 198.5 to 8456.3 ± 456.2 ng h/mL, corresponding to a 2.48-fold increase, indicating substantially greater systemic exposure following PSG-NS administration than Prasita®. PSG-NS also produced significantly greater inhibition of ADP-induced platelet aggregation (78.0 ± 4.2%) than Prasita® (42.0 ± 3.1%; p < 0.01). In the ferric chloride-induced arterial thrombosis model, the PSG-NS group exhibited a prolonged thrombotic occlusion time. The enhanced systemic exposure was associated with an improved antiplatelet response; however, interpretation of the pharmacokinetic findings is limited because the analysis quantified the PSG-related analyte rather than its pharmacologically active metabolite. Cyclodextrin-based nanosponges significantly improved the oral pharmacokinetic profile and antiplatelet activity of PSG by enhancing absorption and systemic exposure without substantially altering elimination kinetics. These findings highlight the potential of nanosponge-mediated delivery as a promising strategy for improving prasugrel therapy, reducing dose requirements, and enhancing therapeutic activity.