Effects of polyethylene glycols on intestinal efflux pump expression and activity in Caco-2 cells

• Main Authors: Darya Hodaei (Author), Behzad Baradaran (Author), Hadi Valizadeh (Author), Parvin Zakeri-Milani (Author)
• Format: Book
• Published: Universidade de São Paulo, 2015-09-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 2175-9790; 10.1590/S1984-82502015000300026
• Keywords: Glicoproteína-P/atividade; Glicoproteína-P/; Caco-2; Rodamina-123; Excipientes; Fármacos/biodisponibilidade; Polietilenoglicol/efeitos; Pharmacy and materia medica; RS1-441
• Source: Brazilian Journal of Pharmaceutical Sciences, Vol 51, Iss 3, Pp 745-753 (2015)

The present study was planned to investigate the influence of polyethylene glycols (PEGs) on the activity and expression of P-glycoprotein (P-gp). Sub-toxic concentrations of PEGs in Caco-2 cells were determined using the MTT test assay. Then the measurement of Rhodamine-123 (Rho-123) uptake, a P-gp fluorescence substrate, in Caco-2 cells confronting PEG 400 (1% and 2% w/v), PEG 4000 (2% and 4% w/v), PEG 6000 (2% and 4% w/v), PEG 10000 (2% and 4% w/v), PEG 15000 (1% and 2% w/v), and PEG 35000 (2% and 4% w/v) overnight was taken to elucidate whether non-toxic concentrations of PEGs are able to impact P-gp activity. Furthermore, western blotting was carried out to investigate P-gp protein expression. The results showed that PEG 400 at concentrations of 1% (w/v) and 2% (w/v) and PEG 6000 at the concentration of 4% (w/v) are notably capable of blocking P-gp. Based on the obtained results it is concluded that the mentioned excipients could be used to obstruct P-gp efflux transporter in order to increase the bioavailability of co-administered substrate drug.