Application of membrane permeability evaluated in in vitro analyses to estimate blood-retinal barrier permeability

Yoshiyuki Kubo, Eri Fukui, Shin Ichi Akanuma, Masanori Tachikawa, Ken Ichi Hosoya

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

The relationship between the in vitro membrane permeability and systemic blood-retinal barrier (BRB) permeability of drugs was investigated. To determine membrane permeability trend lines in this relationship, the apparent permeability (Papp) and initial uptake rate (V) of 23 compounds were evaluated in a parallel artificial membrane permeability assay and the uptake study with a rat retinal endothelial cell line (TR-iBRB2 cells) for comparison with their retinal uptake index (RUI). The RUI values of compounds undergoing passive diffusion across the BRB were correlated with a log of the Papp [RUI = 7.93 × 10 × exp (0.994 × log Papp), r2 = 0.660] and a log of the V [RUI = 26.5 × exp (1.55 × log V), r2 = 0.581]. The RUI values of compounds undergoing carrier-mediated transport across the BRB were correlated with a log of the V [RUI = 26.5 × exp (0.887 × log V), r2 = 0.559]. These results showed that the membrane permeability trend lines derived from the RUI and V values reflect the transport of drugs at the BRB, suggesting that an in vitro analysis-based estimation of the BRB permeability can be obtained using TR-iBRB2 cells and membrane permeability trend lines.

Original languageEnglish
Pages (from-to)2596-2605
Number of pages10
JournalJournal of Pharmaceutical Sciences
Volume101
Issue number7
DOIs
Publication statusPublished - 2012 Jul

Keywords

  • Membrane transport
  • Membrane transporter
  • Passive diffusion/transport
  • Permeability
  • Retinal drug delivery
  • in vitro/in vivo correlations (IVIVC)

ASJC Scopus subject areas

  • Pharmaceutical Science

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