Effect of Pluronic on Cellular Accumulation of Rhodamine 123， a P-gp Substrate in Caco-2 Cells

GUN Yn-in;ZUO Ln;RO Zi-cho;SI Lu-qin;LI Go

Chinese Pharmaceutical Journal ›› 2011, Vol. 46 ›› Issue (12) : 937-942.

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PDF(1445 KB)
Chinese Pharmaceutical Journal ›› 2011, Vol. 46 ›› Issue (12) : 937-942.

Effect of Pluronic on Cellular Accumulation of Rhodamine 123， a P-gp Substrate in Caco-2 Cells

  • GUAN Yan-bin， ZUO Lan， RAO Zi-chao， SI Lu-qin， LI Gao*
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Abstract

OBJECTIVE To determine whether Pluronic， P123， F127， P85， F68 and L61 possess ability to modulate P-glycoprotein(P-gp mediated efflux of drugs. METHODS Caco-2 cell viability was measured using MTT assay in the presence of Pluronic at different concentrations. To evaluate the effects of Pluronic and verapamil（inhibitor of P-gpon cellular drug accumulation in caco-2 cells， rhodamine 123(R-123， a P-gp substrate， was selected as fluorescent probe. A HPLC-fluorescence method was used to determined the concentration of R-123 in Caco-2 cells. Caco-2 cell membranes were exposed to various Pluronic solutions（P123 or F127， and then the ATPase activity of P-gp was assayed by determining liberated inorganic phosphate. RESULTS The viability of Pluronic-treated cells was above 80% except L61， which suggested that Caco-2 cells could maintain their viability under the experiment conditions. In the presence of verapamil and Pluronic at concentrations ranging from 0.00 1-50 mg·mL-1， R-123 accumulation were increased significantly to differernt extent. R-123 accumulation reached maximum levels when Pluronic concentrations were close to or above the CMC， Higher Pluronic concentrations resulted in a drop in accumulation compared to that of R-123 control. Furthermore， P123 and F127 treatments decreased P-gp ATPase activity in Caco-2 cell membranes expressing P-gp. CONCLUSION Pluronic(F68， F127， P123 and P85 can modulate drug efflux by inhibiting P-gp activity in Caco-2 cell membranes. It may be possible to improve the oral bioavailability of P-gp substrates by co-administration of Pluronic.

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Pluronic / P-gp / rhodamine 123 / Caco-2 cell

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GUN Yn-in;ZUO Ln;RO Zi-cho;SI Lu-qin;LI Go. Effect of Pluronic on Cellular Accumulation of Rhodamine 123， a P-gp Substrate in Caco-2 Cells[J]. Chinese Pharmaceutical Journal, 2011, 46(12): 937-942

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