Cilnidipine loaded poly (ε-caprolactone) nanoparticles for enhanced oral delivery: optimization using DoE, physical characterization, pharmacokinetic, and pharmacodynamic evaluation

Cilnidipine (CND), an anti-hypertensive drug, possesses low oral bioavailability due to its poor aqueous solubility, low dissolution rate, and high gut wall metabolism. In the present study, an attempt has been made to prepare CND loaded polycaprolactone based nanoparticles (CND-PCL-NPs) by nanoprecipitation method applying the concepts of Design of Experiments. Critical factors affecting particle size and loading efficiency (LE%) were assessed by a hybrid design approach, comprising of Mini Run Resolution IV design followed by Box-Behnken design. Particle size, PDI, zeta potential and LE% of optimized formulations of CND-PCL-NPs were 220.3 +/- 2.6 nm, 0.25 +/- 0.1, -19.5 +/- 0.9 mV, and 46.4 +/- 1.8%, respectively. No significant changes were observed in the physical stability of nanoparticles when stored at 25 degrees C/60% RH over a period of 3 months. Oral pharmacokinetic studies revealed that F-abs of CND-PCL-NPs (0.55) were significantly higher than the CND suspension (0.26). Pharmacodynamic studies have revealed that the mean percent reduction in systolic blood pressure (% Delta SBP) was significantly higher in the case of CND-PCL-NPs (42%) as compared to CND suspension (24%). Optimized CND-PCL-NPs offer great potential in providing higher and sustained antihypertensive effect compared to conventional formulations of CND.

Automated summary

The study successfully prepared Cilnidipine-loaded nanoparticles using a nanoprecipitation method, resulting in improved oral bioavailability and antihypertensive effects compared to conventional formulations.