Fatty acid binding proteins expressed at the human blood-brain barrier bind drugs in an isoform-specific manner

Gordon Shing Yip Lee, Katharina Kappler, Christopher John Porter, Martin Scanlon, Joseph Nicolazzo

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Reverse hexagonal (H 2) liquid crystals formed from selachyl alcohol were demonstrated to sustain the absorption of the poorly water-soluble drug cinnarizine (CZ) after oral administration to rats. When CZ was administered as a bolus lipid solution in selachyl alcohol, the T max was observed to be 23.5 ± 5.9 h, significantly longer than the control suspension (1 h). Administration of selachyl alcohol as dispersed nanoparticles (hexosomes) also resulted in a sustained plasma profile, with drug concentrations maintained from 20 to 40 ng/mL over the first 24 h after administration. Sustained absorption of CZ from the selachyl alcohol hexosomes led to a significant enhancement (p < 0.05) in oral bioavailability (F% = 17%) compared to the control CZ suspension (9%). Analysis of selachyl alcohol hexosomes using small-angle x-ray scattering indicated that neither the presence of CZ (7 mg/g) nor simulated intestinal fluid altered the H 2 nanostructure. Selachyl alcohol is not susceptible to digestion. Prolonged absorption from the selachyl alcohol-based H 2 systems was attributed to the non-digestible nature of the lipid, similar to non-digestible phytantriol cubic (V 2) systems previously reported. Furthermore, the likely presence of non-sink conditions in the gastric compartment provides a drug reservoir requiring gastric emptying to stimulate drug release from the formulation. This study highlights the potential use of non-digestible liquid crystalline systems generally and nanostructured liquid crystalline particles in particular as novel sustained oral drug delivery systems.
Original languageEnglish
Pages (from-to)3432-3446
Number of pages15
JournalPharmaceutical Research
Issue number10
Publication statusPublished - 2015


  • Drug delivery
  • Hexagonal phase
  • Liquid crystal
  • Nanostructured particles
  • Selachyl alcohol
  • Sustained release

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