Tetronic ^® 904-Containing Polymeric Micelles Overcome the Overexpression of ABCG2 in the Blood–Brain Barrier of Rats and Boost the Penetration of the Antiretroviral Efavirenz into the CNS

Abstract

Tetronic 904-containing polymeric micelles overcame the overexpression of ABCG2 in the BBB caused by chronic administration of EFV then boosting its penetration into the CNS.

Induction of ABCG2/BCRP restricts the distribution of zidovudine to the fetal brain in rats

“…In this sense, no histologic alterations, at least at striatal level, were found in fetal brains exposed in utero to AZT in our model (Fig 1 C and F). An induction of ABCG2 could be attained by sustained substrate exposure, as we previously observed for the overexpression of ABCG2 in small intestine and blood-brain barrier caused by efavirenz (Peroni et al, 2011;Roma et al, 2015) as well as in the placenta and in the fetal brain (present work, Fig 1A and 1B). Moreover, immunofluorescence showed that an specific mark for ABCG2 localized in blood vessels structures in the cortex fetal brain ( Fig 1C-F; (Ek et al, 2010) confirms the presence of this transporter in the developing brainbarrier exerting efflux mechanisms.…”

“…Moreover, it was shown that the efflux of antiretroviral drugs by ABCG2 seems to become of relevance whether a high density of molecules are present in the cell membrane, as occurred either in transfected or transformed cell lines (Pan et al, 2007;Wang et al, 2004Wang et al, , 2003Weiss et al, 2007) or under in vivo repeated exposure to a substrate as efavirenz (Peroni et al, 2011;Roma et al, 2015).…”

“…dose of 60 mg AZT/kg body weight in termpregnancy rats chronically exposed to either the drug or the vehicle in control conditions of after a 30 min-pre administration of the selective inhibitor of ABCG2 gefitinib [20 mg/kg i.p. ; (Roma et al, 2015)]. Drug levels were quantified in maternal blood as well as in fetal brain at different times by HPLC-UV.…”