Preclinical evaluation of cilnidipine nanosponges for enhanced oral bioavailability and sustained antihypertensive...

The present study aimed to evaluate the pharmacokinetic and pharmacodynamic performance of an optimized Cilnidipine-loaded nanosponge (CIL-NS) for oral administration and to compare its bioavailability with a conventional marketed CIL tablet formulation.

CIL-NS were administered orally to male wistar rats at a dose equivalent to 10mg/kg and compared with a marketed CIL tablet suspension (Cilacar®). Plasma drug concentrations were quantified and analyzed using non-compartmental and compartmental pharmacokinetic models. Pharmacodynamic efficacy was assessed using the L-NAME-induced hypertensive rat model.

The CIL-NS demonstrated significantly greater systemic exposure than the conventional tablet. CIL-NS achieved a higher C_max (892.4±45.2ng/mL) at a shorter T_max [1(1-2)h] than the tablet (363.6±23.5ng/mL at 2 (1-4)h; P<0.001). AUC_0-ꚙ was increased 2.65-fold (6124.8±312.7ng·h/mL), resulting in a significant enhancement as compared to the marketed tablet formulation. Mean residence time was significantly prolonged (11.2±1.1h), while elimination half-life remained comparable between formulations. Pharmacodynamically, CIL-NS produced significantly greater reduction in systolic blood pressure (45.1±3.2%) with prolonged antihypertensive activity up to 72±4.6h compared with the marketed formulation (24.4±2.1%; 36±3.8h, respectively; P<0.001). Furthermore, a strong in vitro-in vivo correlation (R²=0.9567) demonstrated a significant correlation between cumulative in vitro drug release and in vivo plasma drug concentration, supporting the predictive relevance of the optimized nanosponge formulation.

CIL-NS significantly improved oral bioavailability with a 2.65-fold increase in systemic exposure, prolonged drug release, and enhanced antihypertensive efficacy without altering elimination kinetics, thereby demonstrating its potential as a promising oral nanosponge delivery system for dose reduction and improved patient compliance in hypertension management.