Effect of poloxamer 188 on lymphatic uptake of carvedilol-loaded solid lipid nanoparticles for bioavailability enhancement

摘要

The present work aimed to investigate the effect of different concentrations of poloxamer 188, a surfactant, on lymphatic uptake of carvedilol-loaded solid lipid nanoparticles (SLNs) for oral bioavailability enhancement. Microemulsion technique was employed to prepare the SLN formulations having varying concentrations of poloxamer 188, which were subsequently subjected to various in vitro and in vivo evaluations to study their release pattern. On increasing the percentage concentration of poloxamer 188, the bioavailability decreased from 4.91-to 2.84-fold after intraduodenal administration in the male Wister rat. It could be attributed to the increase in particle size as well as reduction in hydrophobicity of SLNs. As indicated by pharmacokinetic data, the AUC(0-t) of all three (SLN) formulations (6.27 ±0.24 ugh/mL with FZ-1,4.13± 0.11 ugh/mL with FZ-2, and 3.63 ± 0.10 ugh/mL with FZ-3) were significantly higher (p < 0.05) than that of carvedilol suspension (1.27 ±0.23 ugh/mL). These findings augur well with the possibility of enhancement of the oral bioavailability of drug, via the lymphatic system bypassing hepatic first pass metabolism.