PCM-11: MORPHINE MODULATES DOXORUBICIN UPTAKE: CYTOFLUORIMETRIC STUDY ON AN IN VITRO MODEL OF BLOOD-BRAIN BARRIER

The blood-brain barrier (BBB) is a protective mechanism designed to prevent toxins, both endogenous and exogenous, from damaging the Central Nervous System. In protecting the brain, however, the BBB also serves to prevent therapeutic drugs from entering, thus hampering efficacy. High expression levels of ATP binding cassette (ABC) transporters, P-glycoprotein (Pgp), MRP1 and Breast cancer resistant protein (BCRP), at the brain capillary endothelium suggest they play a major role in preventing drug uptake in the brain. In particular, P-gp exhibits a broad substrate specificity interacting with a wide range of molecules, as doxorubicin (Dox) and morphine. We investigated the influence of morphine on the cellular uptake of Dox by parental and P-gp transfected MDCKII cells as in vitro BBB model. Data showed a Dox accumulation in MDCKII parental cells, without statistically significant difference between Dox alone and Dox plus morphine groups. On the contrary, fluorescence data on MDCKII P-gp cells indicated no Dox accumulation in both control and Dox groups. Dox amount increased in MDCKII P-gp cells when administered in presence of morphine. The Dox level was significantly higher comparing control group (3.84) vs Dox plus morphine group (12.29, P < 0.05). Our results revealed that MDCKII P-gp cells treated with Dox plus morphine presented higher amount of intracellular Dox, demonstrating the effect of morphine on drug efflux pump and suggesting the possibility that morphine enhances the passage of Dox through functional inhibition of P-gp on BBB.