TY - JOUR
T1 - Interactions between human multidrug resistance related protein (MRP2; ABCC2) and excipients commonly used in self-emulsifying drug delivery systems (SEDDS)
AU - Li, Liang
AU - Yi, Tao
AU - Lam, Christopher Wai Kei
N1 - Funding Information:
This study was financially supported by the Science and Technology Development Fund of Macau (No. 003/2011/A ).
PY - 2013/4/15
Y1 - 2013/4/15
N2 - The aim of this study was to investigate the multidrug resistance related protein-2 (MRP2) inhibition effect of excipients commonly employed in the formulation of self-emulsifying drug delivery systems (SEDDS). Cytotoxicity and safe dosages of fifteen excipients, including five surfactants, three oils, three co-surfactants and four solid carriers, were compared using MTT assay. Caco-2 cell permeability and MRP2 vesicles transport assays were used in the inhibition analysis. Scutellarin was shown to be a substrate of MRP2 and used as a probe in the inhibition assay. Twelve excipients decreased efflux ratio of scutellarin in Caco-2 model, among them six excipients showed inhibition effect on MRP2 in MRP2 transport model. In Caco-2 model, Cremophor® EL, Maisine® 35-1, PEG 2000 and β-cyclodextrin reduced efflux ratio of scutellarin the most in the four different excipients groups. The efflux reduction mechanism was further validated by MRP2 transport assay in inhibiting MRP2 activity in Cremophor® EL and PEG 2000. It is suggested that scutellarin quantified by LC-MS can be used as a model drug for MRP2 inhibition analysis using Caco-2 permeability and vesicles transport analyses. Together they constitute a sensitive and rapid screening method for assessing interactions between excipients and MRP2 in SEDDS formulation.
AB - The aim of this study was to investigate the multidrug resistance related protein-2 (MRP2) inhibition effect of excipients commonly employed in the formulation of self-emulsifying drug delivery systems (SEDDS). Cytotoxicity and safe dosages of fifteen excipients, including five surfactants, three oils, three co-surfactants and four solid carriers, were compared using MTT assay. Caco-2 cell permeability and MRP2 vesicles transport assays were used in the inhibition analysis. Scutellarin was shown to be a substrate of MRP2 and used as a probe in the inhibition assay. Twelve excipients decreased efflux ratio of scutellarin in Caco-2 model, among them six excipients showed inhibition effect on MRP2 in MRP2 transport model. In Caco-2 model, Cremophor® EL, Maisine® 35-1, PEG 2000 and β-cyclodextrin reduced efflux ratio of scutellarin the most in the four different excipients groups. The efflux reduction mechanism was further validated by MRP2 transport assay in inhibiting MRP2 activity in Cremophor® EL and PEG 2000. It is suggested that scutellarin quantified by LC-MS can be used as a model drug for MRP2 inhibition analysis using Caco-2 permeability and vesicles transport analyses. Together they constitute a sensitive and rapid screening method for assessing interactions between excipients and MRP2 in SEDDS formulation.
KW - Caco-2
KW - Excipients
KW - MRP2
KW - Membrane vesicles transport assay
KW - SEDDS
UR - http://www.scopus.com/inward/record.url?scp=84875161513&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2013.02.016
DO - 10.1016/j.ijpharm.2013.02.016
M3 - Article
C2 - 23462368
AN - SCOPUS:84875161513
SN - 0378-5173
VL - 447
SP - 192
EP - 198
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1-2
ER -