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

Abstract

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.

Approaches for enhancing oral bioavailability of peptides and proteins

“…Recently, cell penetrating peptides (CPP) have gained a lot of attention in the delivery of small molecules as well as macromolecules, liposomes and nanoparticles into cells by chemical modifications (Chen et al, 2012; Khafagy el and Morishita, 2012; Koren and Torchilin, 2012). CPPs act by transporting their cargoes into the cytoplasm via perturbation of the lipid bilayer of the cell membrane or by endocytosis (Trehin and Merkle, 2004; Zorko and Langel, 2005).…”

Nanostructured Lipid Carriers: Versatile Oral Delivery Vehicle

“…However, it has been documented that modification of lipid nanoparticles for instance biotin attachment over their surface or charge modification promotes cellular uptake of nanoparticles via intestinal cells, overcoming the mucosal barrier that otherwise hinders their uptake [31,35]. Also, studies on cell-penetrating peptides (CPPs) coated over the surface of lipid nanoparticles are also based on the hypothesis that they will promote cross of intact nanoparticles across GIT, which gain access in systemic circulation where reticuloendothelial system (RES) system plays role [73]. However, in vivo studies on engineered NLCs are not satisfactory and there is necessity of detailed future studies to determine effects of composition, physiochemical properties and surface modification on the fate of lipid nanoparticles.…”

“…Interesting studies using CPPs that can recognize specific receptors on GIT cells have allowed scientists to utilize them as an effective tool for oral delivery of various drugs. Although the exact mechanism of CPPs attached/coated lipid nanoparticles is unknown, but it has been considered that CPPs either encounters receptor mediated pathway, thus facilitating the internalization processes via endocytosis and translocation of attached nanoparticles or enter by disrupting the intestinal membrane [73]. In a study, in situ intestinal perfusion model performed in rats showed that peptide-coated NLCs markedly increased absorption of tripterine in the duodenum and jejunum in comparison to noncoated NLCs and tripterine suspension, in other words, 1.5- and 2.9-fold, respectively.…”

“…In a study, in situ intestinal perfusion model performed in rats showed that peptide-coated NLCs markedly increased absorption of tripterine in the duodenum and jejunum in comparison to noncoated NLCs and tripterine suspension, in other words, 1.5- and 2.9-fold, respectively. The relative oral bioavailability in beagles was also found to be higher for peptide coated NLCs [73]. More recently, biotin-conjugated NLCs showed augmentation in oral bioavailability of oridonin in rats, in comparison to nonmodified ones, which was attributed to receptor mediated transport.…”

In situ gel loaded with curcumin-based fluvastatin nanostructured carrier effective against squamous tongue carcinoma

“…The stability of optimized FT-CR NLC formulation could be attributed to the fact that FT was completely dissolved in the lipid matrix. (Zhang et al, 2010) Furthermore, Tween 80 and TPGS reduced the electrostatic repulsion between particles, leading to better stabilization and forming a layered structure around the particles (Zhou, 2012;Yuan et al, 2012).…”