Shah, Pranav
Chavda, Kejal
Vyas, Bhavin
Patel, Shailaja
Article History
First Online: 17 August 2020
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: The Caco-2 cell monolayer model bears close resemblance to human intestinal barrier properties. Therefore, this model finds widespread applications in prediction of in vivo permeability and absorption. Bidirectional (AP → BL and BL → AP) transport analysis using the Caco-2 cell monolayer model is the gold standard to evaluate substrates and inducers/inhibitors of P-gp transporters [CitationRef removed]. In order to compare the intestinal permeability, LGP-SOL and LGP-SLNs were evaluated using the Caco-2 cell monolayers (Fig. InternalRef removed). The cells were cultured in the Transwell® for 21 days for monolayer formation, which was confirmed by a TEER cut-off value of 250 Ω cm<sup>2</sup>. As shown in Fig. InternalRef removed, the observed mean <i>P</i><sub><i>app</i></sub> (AP → BL) values of LGP-SOL and LGP-SLNs were 0.87 × 10<sup>−6</sup> and 2.09 × 10<sup>−6</sup> cm/s, respectively.Absorptive permeability <i>P</i><sub><i>app</i></sub> (AP → BL) of LGP from LGP-SLNs was significantly (<i>p</i> < 0.01) increased (2.4-fold) than LGP-SOL. The possible explanation for the enhancement of transepithelial permeability of LGP by LGP-SLNs formulation is due to poloxamer 188 and Tween 80, both of which are known P-gp inhibitors and hence assisted in increasing the intestinal permeability of LGP [CitationRef removed] .The observed mean <i>P</i><sub><i>app</i></sub> (BL → AP) values of LGP-SOL and LGP-SLNs were 1.59 × 10<sup>−6</sup> and 2.04 × 10<sup>−6</sup> cm/s, respectively. The secretory permeability of LGP-SOL was 1.83-folds higher than absorptive permeability, suggesting higher efflux permeability compared with its influx component. The ratio of <i>P</i><sub><i>app</i></sub> (BL → AP) (secretion component) and <i>P</i><sub><i>app</i></sub> (AP → BL) (absorption component) is defined as efflux ratio (ER). The ER of LGP-SOL and LGP-SLNs were 1.828 and 0.976, respectively. An ER higher than unity suggested a net efflux transport, whereas ER near to unity indicated that LGP excretion from LGP-SLNs is reduced and the amount absorbed is increased. Thus, it was confirmed that the addition of poloxamer 188 and Tween 80 in the preparation of LGP-SLNs increased the intestinal permeability of the LGP. These results are in confirmation with our findings of single-pass perfusion and everted sac studies.
: The authors declare that they have no conflicts of interest.
: All institutional and national guidelines for the care and use of laboratory animals were followed.