Improvement in antihypertensive and antianginal effects of felodipine by enhanced absorption from PLGA nanoparticles optimized by factorial design

Abstract

Objective of the present investigation was to enhance the bioavailability of felodipine by targeting the M cells of Peyer's patches using PLGA nanoparticles (NPs). Felodipine exhibits poor bioavailability due to limited aqueous solubility and extensive first pass metabolism. NPs were prepared using nanoprecipitation and optimized by 3(2) factorial design. Particle size (PS) and entrapment efficiency (% EE) were dependent on Drug/PLGA ratio (X1) and Pluronic F-68 (X2) concentration. % EE, PS and Zeta potential for optimized batch were 91.56±3.21%, 161.3±2.23 nm and -25.7±2.52 mV respectively. DSC, XRD and FTIR studies confirmed compatibility of PLGA and drug. TEM image confirmed the spherical shape. The in vitro and ex vivo studies using rat stomach and intestinal segment confirmed sustained release from NPs. Pharmacodynamic studies in rats showed control of blood pressure and ECG changes for extended duration. Hence, NPs can be a suitable alternative to the current available therapy in hypertension and angina by enhancing the bioavailability.

Keywords: % entrapment efficiency; (% EE); (DSC); (FD); (FTIR); (NPs); (PS); (TEM); (XRD); Bioavailability enhancement; Differential Scanning Calorimetry; Ex vivo; Factorial design; Fourier Transform Infrared spectroscopy; Nanoparticles; Pharmacodynamic studies; Transmission Electron Microscopy; X-ray diffraction; felodipine; nanoparticles; particle size.