title: Effect of cell-penetrating peptide-coated nanostructured lipid carriers on the oral absorption of tripterine.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, People's Republic of China. ychen202@yahoo.com.cn
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Ling
authors.initials: L
authors.lastname: Yuan
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.forename: Zhen-hai
authors.initials: ZH
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Wu
mesh_terms: D000042:Absorption / Q000187:drug effects; D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D001682:Biological Availability; D018938:Caco-2 Cells; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage* / Q000737:chemistry; D018592:Cross-Over Studies; D004285:Dogs; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D049329:Nanostructures / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D053978:Pentacyclic Triterpenes; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014315:Triterpenes / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; C050414:celastrol