Effect of cell-penetrating peptide-coated nanostructured lipid carriers on the oral absorption of tripterine

Purpose: To develop nanostructured-lipid carriers (NLCs) coated with cell-penetrating peptides (CPP) for improving the oral bioavailability of tripterine. Methods: We prepared CPP-coated tripterine-loaded NLCs (CT-NLCs) by using a solvent evaporation method, and determined their physical properties. In vitro drug release was determined by using a dialysis bag diffusion technique, and intestinal toxicity was evaluated by performing MTT assay using Caco-2 cells. In vivo absorption was studied in an in situ rat intestinal perfusion model, and oral bioavailability was examined in beagles. Results: The average particle size, zeta potential, and encapsulation efficiency of the optimized CT-NLCs were 126.7 +/- 9.2 nm, 28.7 +/- 3.4 mV, and 72.64% +/- 1.37%, respectively. The CT-NLCs showed a controlled release profile in vitro and had significantly lower intestinal cytotoxicity than the tripterine solution (P < 0.05). The absorption levels of tripterine from the CT-NLCs in the rat duodenum and jejunum were markedly higher than with tripterine-loaded NLCs without the CPP coating (T-NLCs), and with tripterine solution. Pharmacokinetic study showed that the maximum concentration of the CT-NLCs was greater than that of the T-NLCs and tripterine suspension, and that the time to maximum concentration of the CT-NLCs as well as the T-NLCs, was longer than that of the tripterine suspension. The relative oral bioavailability of the CT-NLCs compared to that of tripterine suspension and T-NLCs were 484.75% and 149.91% respectively. Conclusion: The oral bioavailability of tripterine is dramatically increased by CT-NLCs. Therefore, CT-NLCs seem to be a promising carrier for oral delivery of tripterine.