Comparative study of nisoldipine-loaded nanostructured lipid carriers and solid lipid nanoparticles for oral delivery: preparation, characterization, permeation and pharmacokinetic evaluation

摘要

Nisoldipine (ND) has low oral bioavailability (5%) due to first-pass metabolism. Previously, solid lipid nanoparticles (SLNs) of ND were reported. In this study, nanostructured lipid carriers (NLCs) of ND are developed to enhance the oral bioavailability. ND-NLCs were prepared using hot homogenization-ultrasonication method, using oleic acid and trimyristate as liquid lipid and solid lipid, respectively. Prepared NLCs are evaluated for an optimal system using measuring size, zeta potential, entrapment efficiency, in-vitro release and in-situ absorption studies. Further, in vivo pharmacokinetic (PK) studies of NLC were conducted in rats comparison with SLN and suspension as controls. Size, ZP and EE of optimized NLCs were found to be 110.4 +/- 2.95 nm, -29.4 +/- 2.05 mV and 97.07 +/- 2.27%, respectively. Drug loaded into NLCs was converted to amorphous form revealed by differential scanning calorimeter (DSC) and X-ray diffractometry (XRD) technique and nearly spherical in shape by scanning electron microscopy (SEM) studies. Drug release and absorption of ND were prolonged from ND-NLCs and ND-SLNs. From the PK results, NLCs showed 2.46 and 1.09-folds improvement in oral bioavailability of ND compared with suspension and SLNs formulations, respectively. Taken together, the NLCs and SLNs are used as carriers for the enhancement of oral bioavailability of the ND.