Pharmacokinetics, tissue distribution and bioavailability of nitrendipine solid lipid nanoparticles after intravenous and intraduodenal administration.

PURPOSE

The aim of this research was to study whether the bioavailability of nitrendipine (NDP) could be improved by administering nitrendipine solid lipid nanoparticles (SLN) duodenally to rats.

METHODS

Nitrendipine was incorporated into SLN prepared by hot homogenization followed by ultrasonication method. SLN were produced using various triglycerides (trimyristin, tripalmitin and tristearin), soy phosphatidylcholine 95%, poloxamer 188 and charge modifiers (dicetyl phosphate, DCP and stearylamine, SA). Particle size and charge measurements were made with a Malvern Zetasizer. Pharmacokinetics of nitrendipine SLNs (NDP-SLNs) after intravenous (i.v.) and intraduodenal (i.d.) administration to conscious male Wistar rats were studied. Tissue distribution studies of NDP-SLNs were carried out in Swiss albino mice after i.v. administration and compared to nitrendipine suspension (NDP-Susp).

RESULTS

Average size and zeta potential of SLNs of different lipids, with and without charge modifiers ranged from 101.9 +/- 3.0 to 123.5 +/- 3.0 nm and - 35.1 +/- 0.5 to +34.6 +/- 2.3 mV, respectively. AUC(0-infinity) was increased (up to 4.51-folds) and clearance was decreased (up to 4.54-folds) after i.v. administration of NDP-SLNs with and without charge modifiers compared to NDP-Susp. Effective bioavailability of NDP-SLNs were 2.81-5.35-folds greater after i.d. administration in comparison with that of NDP-Susp. In tested organs, the AUC and MRT of NDP-SLNs were higher than those of NDP-Susp especially in brain, heart and reticuloendothelial cells containing organs.

CONCLUSIONS

SLN are suitable drug delivery systems for the improvement of bioavailability of nitrendipine. Negatively and positively charged SLN were better taken up by the liver and brain, respectively.